Gist (guz podścieliskowy przewodu pokarmowego)

Gist (guz podścieliskowy przewodu pokarmowego)
Leczenie

Chirurgiczna resekcja pozostaje podstawową metodą leczenia zlokalizowanych nowotworów podścieliskowych przewodu pokarmowego (GIST), z celem uzyskania całkowitego usunięcia guza z ujemnymi marginesami mikroskopowymi (R0). W przypadku guzów mniejszych niż 5 cm, zwłaszcza zlokalizowanych w żołądku i jelicie cienkim, preferowane są techniki minimalnie inwazyjne, takie jak laparoskopia. Dla guzów miejscowo zaawansowanych konieczna może być resekcja en bloc obejmująca sąsiednie narządy. Terapia neoadjuwantowa imatynibem (standardowa dawka 400 mg/dobę, 800 mg/dobę dla mutacji KIT eksonu 9) jest stosowana w celu zmniejszenia guza przed operacją, zwłaszcza w przypadkach dużych lub trudno dostępnych zmian. W leczeniu zaawansowanych, przerzutowych lub nawrotowych GIST, terapia celowana inhibitorami kinazy tyrozynowej (TKI) stanowi standard, z imatynibem jako lekiem pierwszego rzutu, sunitynibem i regorafenibem jako terapiami kolejnych linii, a awapritynibem dedykowanym mutacji PDGFRA D842V. Ripretynib jest wskazany w leczeniu czwartego rzutu u pacjentów z progresją po trzech lub więcej TKI.

Chirurgiczne leczenie nowotworów podścieliskowych przewodu pokarmowego (GIST)

Chirurgiczna resekcja jest podstawową metodą leczenia pacjentów z nowotworami podścieliskowymi przewodu pokarmowego (GIST), które nie rozprzestrzeniły się do innych części ciała. Celem operacji jest całkowite usunięcie guza wraz z nienaruszoną pseudotorebką i uzyskanie ujemnych marginesów mikroskopowych¹. Jest to jedyna metoda dająca szansę na całkowite wyleczenie²³.

Zakres operacji zależy od wielkości i lokalizacji guza oraz ogólnego stanu zdrowia pacjenta. W przypadku małych guzów, techniki minimalnie inwazyjne, takie jak laparoskopia, są coraz częściej stosowane⁴⁵. Laparoskopowe usunięcie jest zalecane w przypadku guzów mniejszych niż 5 cm, zlokalizowanych w żołądku i jelicie cienkim⁶.

Dla guzów miejscowo zaawansowanych, naciekających okoliczne narządy, może być konieczna resekcja en bloc obejmująca zajęte narządy, takie jak okrężnica, śledziona czy wątroba⁷. Wyniki leczenia nie są zależne od rodzaju resekcji (klinowa resekcja vs. gastrektomia), pod warunkiem wykonania całkowitej resekcji (R0)⁷.

W przypadku guzów dużych, trudno dostępnych lub zlokalizowanych w miejscach, gdzie radykalna operacja mogłaby spowodować znaczne uszkodzenie narządów, stosuje się terapię neoadjuwantową inhibitorami kinazy tyrozynowej, najczęściej imatynibem, w celu zmniejszenia guza przed operacją¹⁸.

Leczenie chirurgiczne w chorobie zaawansowanej

W przypadku choroby rozsianej, rozważana jest resekcja paliatywna, ponieważ opisywano długotrwałe przeżycia w niektórych przypadkach⁷. Dzięki zdolności imatynibu do uczynienia operacyjnymi pierwotnie nieoperacyjnych guzów GIST, istnieje rola dla chirurgii cytoredukcyjnej (resekcja R0 lub R1) w leczeniu nawrotowej choroby przerzutowej ograniczonej do jamy brzusznej⁷.

Pacjenci z zaawansowanymi GIST, którzy mają ograniczoną progresję lub stabilną chorobę pod wpływem terapii celowanej, doświadczają wydłużonego całkowitego przeżycia, gdy dodatkowo poddani są operacji usunięcia większości pozostałego nowotworu, a następnie kontynuują terapię celowaną⁹.

Do 70% pacjentów, u których możliwe jest wykonanie resekcji R0/R1 w warunkach stabilnej lub częściowo reagującej choroby, cieszy się przeżyciem wolnym od progresji do 4 lat po rozpoczęciu terapii imatynibem¹⁰.

Terapia celowana w leczeniu GIST

Terapia celowana z wykorzystaniem inhibitorów kinazy tyrozynowej (TKI) stanowi główną metodę leczenia farmakologicznego GIST. TKI są wskazane u pacjentów z guzami nieoperacyjnymi, granicznie resekcyjnymi, przerzutowymi lub nawrotowymi. Są również stosowane jako terapia adjuwantowa u pacjentów z GIST o wysokim ryzyku nawrotu¹.

Imatynib

Imatynib (Glivec/Gleevec) jest inhibitorem kinazy tyrozynowej i stanowi leczenie pierwszego wyboru dla większości pacjentów z GIST z mutacjami KIT i PDGFRA¹. Jest stosowany w następujących sytuacjach:

Jako terapia neoadjuwantowa przed operacją w celu zmniejszenia guza¹¹
Jako terapia adjuwantowa po operacji w przypadku guzów o wysokim ryzyku nawrotu¹²
Jako leczenie pierwszego rzutu w przypadku nieoperacyjnych lub przerzutowych GIST¹³

¹⁴

Skuteczność imatynibu jest najwyższa w GIST zawierających mutację w eksonie 11 KIT; około 90% tych pacjentów odpowiada na leczenie¹⁵. Standardowa dawka imatynibu wynosi 400 mg dziennie, jednak dane pokazują, że pacjenci z wariantami KIT eksonu 9 mają lepsze wyniki w zakresie przeżycia wolnego od progresji przy wyższej dawce 800 mg dziennie¹⁶.

Wskaźnik korzyści klinicznej z leczenia imatynibem wynosi około 80%, a mediana przeżycia wolnego od progresji zbliża się do 24 miesięcy, z medianą przeżycia całkowitego wynoszącą prawie 5 lat¹⁷. Imatynib powinien być kontynuowany bezterminowo u pacjentów z chorobą przerzutową, u których nie występuje progresja i którzy dobrze tolerują lek¹⁷.

Leczenie drugiego i trzeciego rzutu

W przypadku progresji guza (lub nietolerancji imatynibu), dane wspierają terapię drugiego rzutu z zastosowaniem albo zwiększenia dawki imatynibu do 800 mg dziennie, albo sunitynibu¹⁴.

Sunitynib (Sutent) to inhibitor wielokinazowy, który blokuje KIT/PDGFR, receptor czynnika stymulującego kolonie 1 (CSF1R), kinazę tyrozynową 3 podobną do Fms, RET i ma działanie antyangiogenne poprzez hamowanie receptorów czynnika wzrostu śródbłonka naczyniowego (VEGFR1-3)¹⁸. Jest stosowany jako leczenie drugiego rzutu u pacjentów, u których wystąpiła progresja podczas leczenia imatynibem lub którzy nie mogą tolerować imatynibu¹⁹.

Regorafenib (Stivarga) jest kolejnym doustnym inhibitorem wielokinazowym, który działa na wiele szlaków zaangażowanych we wzrost guza, w tym angiogenezę nowotworu (VEGFR-1, -2 i -3 oraz TIE2), onkogenezę (KIT, RET, RAF-1, BRAF i BRAFV600E) i mikrośrodowisko guza (PDGFR i receptor czynnika wzrostu fibroblastów (FGFR))¹⁸. FDA zatwierdziła regorafenib do leczenia GIST opornych na leczenie pierwszego rzutu¹⁴.

Leczenie w przypadku specyficznych mutacji

W przypadku pacjentów z GIST charakteryzującymi się mutacją PDGFRA D842V, jako leczenie pierwszego rzutu stosuje się awapritynib, biorąc pod uwagę wysoką korzyść kliniczną i oporność na imatynib w tym podtypie¹²⁰. Awapritynib otrzymał zatwierdzenie FDA w styczniu 2020 roku dla dorosłych z nieoperacyjnym GIST, posiadającym mutacje PDGFRA eksonu 18, w tym mutację D842V²¹.

Ripretynib (Qinlock) jest wskazany dla pacjentów z zaawansowanym GIST, u których występuje progresja choroby (lub którzy nie tolerują) trzech lub więcej TKI, w tym imatynibu¹⁴. Jest to silny inhibitor kontroli kieszeni przełączającej kinaz KIT i PDGFR, wykazujący aktywność przeciwko szerokiemu zakresowi mutacji²¹.

Leczenie adjuwantowe i neoadjuwantowe

Terapia adjuwantowa

Terapia adjuwantowa imatynibem jest standardowym leczeniem dla GIST wysokiego ryzyka po operacji²². Ryzyko nawrotu GIST stratyfikuje się oceniając indeks mitotyczny, wielkość guza i lokalizację guza²².

Badanie kliniczne fazy III (ACOSOG Z9001) potwierdziło rolę adjuwantowego imatynibu (400 mg dziennie) przez 1 rok. Ryzyko nawrotu zostało znacznie zmniejszone o 40% (współczynnik ryzyka [HR], 0,6; 95% CI, 0,43 do 0,75; skorygowane p < 0,001) w ramieniu imatynibu²³.

Adjuwantowa terapia imatynibem przez 3 lata wiązała się z poprawą przeżycia wolnego od nawrotu i przeżycia całkowitego w porównaniu z terapią 1-roczną w randomizowanym badaniu u pacjentów wysokiego ryzyka²⁴. Obecnie zalecany okres terapii wynosi co najmniej 3 lata²⁵.

Terapia neoadjuwantowa

Terapia neoadjuwantowa jest stosowana u pacjentów z GIST, które są podejrzewane o duży rozmiar lub naciekanie innych narządów²². Głównym celem przedoperacyjnej terapii imatynibem jest zmniejszenie rozmiaru guza, maksymalizacja resekcyjności i poprawa jakości życia dzięki uniknięciu resekcji wielonarządowej²³.

Wkład przedoperacyjnej terapii imatynibem różni się w zależności od lokalizacji guza i jest uważany za szczególnie skuteczny w połączeniu przełykowo-żołądkowym, dwunastnicy i odbytnicy²⁵. Bezpieczeństwo i skuteczność neoadjuwantowego imatynibu zostały ustalone w kilku prospektywnych i retrospektywnych badaniach²⁶.

Inne metody leczenia GIST

Metody ablacyjne i embolizacja

W przypadku GIST, które rozprzestrzeniły się do wątroby, a chirurgia nie jest opcją, stosowane mogą być techniki ablacji i embolizacji¹¹. Ablacja wykorzystuje substancje chemiczne, ciepło, zimno, mikrofale lub fale radiowe o wysokiej energii do niszczenia komórek nowotworowych. W embolizacji, lekarz wstrzykuje substancje do naczyń krwionośnych w celu odcięcia dopływu krwi do komórek nowotworowych w wątrobie²⁷.

Jeśli pacjent nie może przejść resekcji chirurgicznej, wówczas może być opcją ablacja radiofalowa (RF) pod kontrolą CT²⁸. Embolizacja tętnicy wątrobowej jest zabiegiem chirurgicznym stosowanym w leczeniu przerzutów do wątroby GIST²⁹.

Obserwacja i leczenie wspomagające

Obserwacja (ang. watchful waiting) to ścisłe monitorowanie stanu pacjenta bez podawania jakiegokolwiek leczenia, dopóki nie pojawią się objawy lub nie ulegną zmianie³⁰. Bardzo małe GIST (mniejsze niż końcówka gumki do ołówka) czasami pozostają takie jak są – ani nie rosną, ani się nie rozprzestrzeniają. W takich przypadkach lekarze mogą zalecić podejście polegające na obserwacji i oczekiwaniu, gdzie guz jest regularnie sprawdzany pod kątem oznak wzrostu³¹.

Leczenie wspomagające jest zwykle stosowane, jeśli GIST pogarsza się podczas leczenia lub występują działania niepożądane³⁰. Może ono obejmować zarządzanie bólem, wsparcie psychologiczne, społeczne i duchowe. Celem jest poprawa jakości życia pacjentów z poważną lub zagrażającą życiu chorobą³².

Chemioterapia i radioterapia

Istnieje powszechna zgoda, że standardowa chemioterapia nie odgrywa roli w podstawowej terapii GIST¹⁴. Standardowa chemioterapia nie jest skuteczna w leczeniu GIST i nie powinna być stosowana³³.

Radioterapia jest rzadko zalecana w przypadku GIST³⁴. Jednak może być stosowana w celu kontrolowania objawów, takich jak ból spowodowany przerzutowym nowotworem³⁵.

Badania kliniczne i nowe kierunki leczenia

Badania kliniczne są jednym ze sposobów na otrzymanie najnowocześniejszego leczenia onkologicznego³⁶. Pacjenci powinni zapytać, czy badania kliniczne są dla nich odpowiednim podejściem³⁷.

Obecnie dostępnych jest kilka obiecujących kierunków badań:

Połączenie TKI z inhibitorami MEK (np. imatynib z binimetynibem) wykazało 69% wskaźnik częściowej odpowiedzi wraz z medianą PFS około 30 miesięcy³⁸
Kombinacje TKI i immunoterapii pokazują obiecujące wyniki³⁹
Bezuklastynib – nowy lek celujący w mutacje w eksonach 17 i 18³⁹
Immunoterapia z użyciem inhibitorów punktów kontrolnych, takich jak niwolumab (samodzielnie lub w połączeniu z ipilimumabem)²⁸

⁴⁰

Pomimo znaczących postępów w leczeniu GIST, oporność na leki pozostaje głównym wyzwaniem. Istnieje potrzeba dalszych badań nad nowymi terapiami i kombinacjami leków⁴⁰.

Personalizacja leczenia GIST

Znaczenie profilowania molekularnego

Terapia celowana GIST znacznie poprawiła rokowanie pacjentów z zaawansowanym GIST w porównaniu z historycznymi metodami leczenia³⁹. Skuteczność inhibitorów kinazy tyrozynowej ukierunkowanych na podstawowe szlaki onkogenne, takie jak KIT, PDGFRA i receptory VEGF, w zaawansowanym GIST potwierdza użyteczność terapii celowanej w nowotworach litych z uzależnieniem od onkogenów⁴¹.

Standardową metodologią stosowaną do molekularnej charakterystyki GIST pozostaje sekwencjonowanie tkanki guza⁴². Te wyniki sugerują, że mutacje genetyczne mają wartość prognostyczną i że grupowanie według mutacji jest przydatne w określaniu wskazań do terapii adjuwantowej; uzupełnia również stratyfikację ryzyka kliniczno-patologicznego⁴³.

Multidyscyplinarne podejście do leczenia

Leczenie GIST zależy od wielkości i lokalizacji guza, wieku i współchorobowości pacjenta oraz obecności lub braku objawów lub powikłań, takich jak perforacja, krwawienie lub niedrożność. Planowanie leczenia multidyscyplinarnego jest niezbędne⁴⁴.

Powinno ono angażować histopatologów, radiologów, chirurgów i onkologów medycznych, a także gastroenterologów i specjalistów medycyny nuklearnej w zależności od potrzeb. Takie zespoły są dostępne w ośrodkach referencyjnych dla mięsaków i GIST, które leczą dużą liczbę pacjentów z GIST rocznie⁴⁴.

Optymalna strategia leczenia powinna być ustalona i wdrożona przez zespół multidyscyplinarny doświadczony w leczeniu mięsaków. Badania molekularne powinny być wykonywane zawsze, gdy to możliwe, ponieważ profil molekularny może różnić się od profilu pacjentów powyżej 40 roku życia i może wpływać na wybór terapii systemowej⁴⁵.

GIST to rzadki nowotwór. Ważne jest, aby pacjenci mieli możliwość spotkania ze specjalistą mięsaków, ponieważ może to dać im możliwość udziału w trwających badaniach klinicznych w tym otoczeniu, o których w przeciwnym razie mogliby nie wiedzieć⁴².

Postępowanie w przypadku nawrotu GIST

Jeśli nowotwór powraca po leczeniu lub odpowiada na leczenie, ale potem powraca, nazywa się to nawrotem. W przypadku większości nawrotów, leczenie inhibitorem kinazy tyrozynowej, takim jak imatynib (Gleevec), jest często pierwszą opcją, aby spróbować zmniejszyć guzy, o ile wciąż jest skuteczny, a pacjent może tolerować jego przyjmowanie⁴⁶.

Gdy GIST powraca po początkowym leczeniu, może powrócić w miejscu, w którym zaczął. Nazywa się to nawrotem miejscowym. Może też powrócić w innej części ciała, co nazywane jest wtórnym lub przerzutowym nowotworem⁴⁷.

GIST, który powraca, jest zwykle leczony terapią celowaną. Operacja może być również opcją, jeśli istnieje tylko jeden mały nowy GIST⁴⁷.

W przypadku nawrotu choroby konieczny jest nowy cykl testów genomowych, aby dowiedzieć się jak najwięcej o nawrocie⁴⁸. Celem medycyny precyzyjnej w nowotworach jest określenie zmian genomowych w DNA GIST, które napędzają wzrost nowotworu⁴⁸.

Jakość życia i opieka wspomagająca

Leczenie GIST może mieć działania niepożądane. Należy rozmawiać z lekarzem, jeśli objawy lub działania niepożądane leczenia utrzymują się lub stają się ciężkie, lub gdy objawy zakłócają życie⁴⁹.

Po operacji mogą rozwinąć się niedobory witamin i minerałów z powodu braku wchłaniania. Dlatego suplementy mogą być pomocne. Należy rozmawiać z lekarzem o tym, które suplementy mogą być korzystne⁴⁹.

Należy zaplanować harmonogram pracy wokół GIST. Pracować elastyczne godziny i robić przerwy. Jeśli to możliwe, wziąć urlop od pracy. Zgodnie z ustawą o urlopach rodzinnych i medycznych, może istnieć możliwość skorzystania z do 12 tygodni urlopu z powodu choroby⁴⁹.

Nawet jeśli wybierzesz niepoddawanie się leczeniu nowotworu, nadal możesz otrzymać opiekę wspomagającą, aby pomóc w bólu lub innych objawach⁵⁰.

Pamiętaj, aby otrzymać opiekę paliatywną, która pomoże złagodzić problematyczne objawy GIST i działania niepożądane oraz poprawić jakość życia podczas leczenia⁵¹.

Podsumowanie aktualnych wytycznych leczenia

Na podstawie aktualnych wytycznych leczenia GIST można podsumować następujące zalecenia:

Dla zlokalizowanego GIST, chirurgia jest standardowym leczeniem i powinna być wykonana zawsze, gdy to możliwe⁴⁸
Celem chirurgii jest całkowite usunięcie guza z nienaruszoną pseudotorebką i ujemnymi marginesami mikroskopowymi⁴⁸
W przypadku GIST wysokiego ryzyka, adjuwantowa terapia imatynibem przez 3 lata po operacji jest standardowym leczeniem²⁵
Dla nieoperacyjnych i przerzutowych GIST, imatynib jest standardowym leczeniem pierwszego rzutu⁵²
Pacjenci, u których występuje progresja lub którzy nie tolerują imatynibu, mogą być leczeni sunitynibem w terapii drugiego rzutu⁵³
Regorafenib jest kolejnym doustnym inhibitorem, który silnie blokuje wiele kinaz białkowych i jest stosowany jako terapia trzeciego rzutu⁵³
Dla dorosłych pacjentów z nieoperacyjnym lub przerzutowym GIST posiadającym mutację PDGFRA D842V, która jest odporna na imatynib, awapritynib został zatwierdzony do terapii pierwszego rzutu⁵³
Ripretynib jest zalecany dla leczenia czwartego rzutu w przypadku zaawansowanego GIST⁵⁴

Dla pacjentów z GIST z mutacjami odpornymi na imatynib, sunitynib, regorafenib, ripretynib i awapritynib, zalecane jest skierowanie do badania klinicznego⁵³.

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Materiały źródłowe

#1 Gastrointestinal Stromal Tumors Treatment (PDQÂ®) – NCI
https://www.cancer.gov/types/soft-tissue-sarcoma/hp/gist-treatment-pdq
Surgical resection is the primary treatment modality for the following types of patients: […] The goal of surgery is complete gross resection with an intact pseudocapsule and negative microscopic margins. […] Neoadjuvant imatinib therapy can be given to patients with large tumors or difficult-to-access GISTs that are considered marginally resectable. […] TKI therapy is indicated for patients with unresectable, borderline resectable, metastatic, or recurrent GISTs. It is also indicated as adjuvant therapy for patients with GISTs at high risk of recurrence. […] The TKI imatinib mesylate is used as first-line therapy for most patients with KIT- and PDGFRA-variant GISTs. […] For patients with GISTs characterized by a PDGFRA D842V variant, avapritinib is used as first-line therapy, given the high clinical benefit and imatinib-resistance in this subtype.
#2 Gastrointestinal stromal tumors (GISTs): What are they, and how are they treated? | MD Anderson Cancer Center
https://www.mdanderson.org/cancerwise/gastrointestinal-stromal-tumors–gists—what-are-they-and-how-are-they-treated.h00-159699123.html
GISTs can be cured if theyre caught early and can be removed by surgery. […] Treatment for GISTs usually involves surgery and/or targeted therapy. […] For GISTs that have not spread to other parts of the body, surgery is used to remove all of the cancer. […] Sometimes, targeted therapy is used to shrink the tumor(s) before surgery. Targeted therapy is also used to treat GISTs that are advanced or have spread to other parts of the body. […] Imatinib works well in 60% to 70% of patients, so it is the first-line treatment for most GISTs. […] If initial treatment doesnt work or stops working, patients may be given sunitinib, a second-line treatment. […] If the cancer doesnt respond to standard treatments, the patient may need to try other targeted therapy drugs or enroll in a clinical trial.
#3 Gastrointestinal Stromal Tumors (GISTs) Treatment & Management: Approach Considerations, Medical Care, Surgical Care
https://emedicine.medscape.com/article/278845-treatment
In January 2020, the FDA approved avapritinib (Ayvakit), another TKI that inhibits PDGFRA. […] Avapritinib targets PDGFRA and PDGFRA D842 mutants as well as multiple KIT exon 11, 11/17, and 17 mutants. […] Ripretinib (Qinlock) was approved for advanced GIST in previously treated patients in May 2020. […] Use of adjuvant TKI therapy after surgical resection is guided by the estimated malignant potential. […] Surgery is the definitive therapy for localized GISTs. […] Despite the proven success of imatinib and other newer tyrosine kinase inhibitors, surgical resection remains the treatment of choice and offers the only chance for cure of GIST. […] The main operative principle is resection of the tumor with negative microscopic margins. […] For small GISTs, local resection may be adequate, if it is technically possible and does not compromise a complete resection.
#4 Current treatment strategies and future perspectives for gastrointestinal stromal tumors
https://pmc.ncbi.nlm.nih.gov/articles/PMC8788163/
Less invasive surgical procedures such as laparoscopy and laparoscopic and endoscopic cooperative surgery (LECS) have been performed for small GISTs, while preoperative chemotherapy is used to improve the probability of complete resection and prognosis for giant GISTs. […] The purpose of this review is to provide an overview of the clinical features, its diverse treatment modalities, and strategies for genetically informed drug therapy of GISTs. […] If GISTs are suspected on endoscopy, imaging, and endoscopic ultrasound (EUS), then an EUS-guided puncture can be performed to confirm the diagnosis. […] When GIST is suspected, the treatment strategy differs depending on whether complete resection is possible. […] For tumors that are not resectable without significant morbidity, administration of neoadjuvant therapy is the appropriate approach.
#5 Gastrointestinal Stromal Tumors (GISTs) Treatment & Management: Approach Considerations, Medical Care, Surgical Care
https://emedicine.medscape.com/article/278845-treatment
Up to 70% of patients able to undergo an R0/R1 resection in the setting of stable or partially responsive disease enjoy a progression-free survival as long as 4 years after the initiation of imatinib therapy. […] Laparoscopic resection is increasingly used for treatment of GISTs. […] Numerous published reports of laparoscopic resection of gastric GISTs have demonstrated the feasibility and safety of this technique.
#6 Gastrointestinal stromal tumors: a comprehensive review – Parab – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/23883/19709
Imatinib mesylate, a selective tyrosine kinase receptor inhibitor (TKI), is used as an adjuvant or neoadjuvant therapy to improve the morbidity and mortality associated with GISTs. […] Due to growing resistance, sunitinib and regorafenib are effective second-line TKIs. […] The gold standard of treatment for GISTs is surgical resection through laparoscopy, however if the patient is unstable then an open laparotomy is the preferred method of treatment. […] Laparoscopic surgery (LSG) is recommended for GISTs that are less than 5cm and located in the stomach and small bowel. […] However, if there is metastatic disease then imatinib should be recommended as the targeted therapy in conjunction with surgery. […] The 3 agents approved for the treatment of GISTs are imatinib (Gleevec), sunitinib (Sutent), and ponatinib.
#7 Gastrointestinal Stromal Tumors (GISTs) Treatment & Management: Approach Considerations, Medical Care, Surgical Care
https://emedicine.medscape.com/article/278845-treatment
For locally invasive tumors, en bloc resection of adjacent involved organs, such as colon, spleen, or liver, may be indicated. […] Recurrence and survival are not associated with the type of resection (wedge resection versus any type of gastrectomy), provided that a complete resection (R0) is performed. […] In cases of disseminated disease, consider palliative resection, because long-term survival has been reported in certain cases. […] Given the ability of imatinib to render initially inoperable GIST tumors resectable, there may be a role for cytoreductive surgery (R0 or R1 resection) in the setting of recurrent metastatic disease confined to the abdomen. […] A significant minority of these patients require liver resections (40%) and the majority require multivisceral resection, including bowel resections, peritonectomy, and/or omentectomy (60%).
#8 Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines | British Journal of Cancer
https://www.nature.com/articles/s41416-024-02672-0
When R0 resection is considered difficult to achieve or is thought likely to result in major functional sequelae, e.g. total gastrectomy or abdominoperineal resection of rectum, neo-adjuvant imatinib should be considered provided there is a potentially sensitive mutation. […] Adjuvant treatment with imatinib for 3 years was associated with improved relapse-free and overall survival compared with 1 year of therapy in a randomised trial in high-risk patients. […] In patients with inoperable and metastatic disease, imatinib is the standard treatment, including patients who had previously received the drug as adjuvant therapy without relapse during this treatment. […] The standard dose of imatinib is 400mg daily. However, data have shown that patients with KIT exon 9 variants fare better in terms of progression-free survival (PFS) on a higher dose of 800mg daily, which is therefore the standard treatment in this subgroup.
#9 Gastrointestinal Stromal Tumors | Nebraska Hematology Oncology – Cancer Care Treatment Blood Disorders Clinical Trials Lincoln Nebraska (NE)
https://www.yourcancercare.com/types-of-cancer/gastrointestinal-stromal-tumors
Patients with advanced GISTs who have limited progression or stable disease with targeted therapy have been shown to experience prolonged overall survival when they also undergo surgery to remove the majority of their remaining cancer, then continue with targeted therapy. […] Tyrosine kinase is a protein that is overproduced in GIST cells as a result of a genetic mutation and is responsible for helping the cancer cells survive and grow. A TKI is a precision cancer medicine that blocks tyrosine kinase activity slowing the growth of the cancer. TKIs are the main medical treatment for GIST. […] Gleevec (imatinib mesylate) was the first TKI approved for treatment and has become the standard initial treatment. […] Sutent (sunitinib): Like Gleevec, Sutent inhibits the tyrosine kinase protein.
#10 Gastrointestinal Stromal Tumors (GISTs) Treatment & Management: Approach Considerations, Medical Care, Surgical Care
https://emedicine.medscape.com/article/278845-treatment
Up to 70% of patients able to undergo an R0/R1 resection in the setting of stable or partially responsive disease enjoy a progression-free survival as long as 4 years after the initiation of imatinib therapy. […] Laparoscopic resection is increasingly used for treatment of GISTs. […] Numerous published reports of laparoscopic resection of gastric GISTs have demonstrated the feasibility and safety of this technique.
#11 Treating Gastrointestinal Stromal Tumors | American Cancer Society
https://www.cancer.org/cancer/types/gastrointestinal-stromal-tumor/treating.html
If you’ve been diagnosed with a gastrointestinal stromal tumor (GIST), your cancer care team will discuss your treatment options with you. It’s important to weigh the benefits of each treatment option against the possible risks and side effects. […] Types of treatment for GIST include: Surgery for Gastrointestinal Stromal Tumors, Targeted Drug Therapy for Gastrointestinal Stromal Tumors, Ablation and Embolization to Treat Gastrointestinal Stromal Tumors, Chemotherapy for Gastrointestinal Stromal Tumors, Radiation Therapy for Gastrointestinal Stromal Tumors. […] Not all GISTs need to be treated right away. But if treatment is needed, the main types used are surgery and targeted therapy. Other treatments, such as ablation, embolization, chemotherapy, and radiation, are used less often. […] The treatment of GISTs can be complex, so its important to be evaluated and treated by a team of doctors who have experience with this type of cancer.
#12 Typical Treatment Options for Gastrointestinal Stromal Tumors | American Cancer Society
https://www.cancer.org/cancer/types/gastrointestinal-stromal-tumor/treating/by-spread.html
Treatment for gastrointestinal stromal tumors (GISTs) depends mainly on factors such as: […] Surgery is the main treatment for most other small tumors. The need for further treatment after surgery depends on the risk of the GIST coming back. […] If the doctor thinks that the cancer has an intermediate or high risk of coming back based on these factors, adjuvant treatment with the targeted drug imatinib (Gleevec) is typically recommended for at least a year after surgery. […] Treatment with the targeted drug imatinib (Gleevec) is usually done first to try to shrink the tumor. […] If imatinib is given, it is continued at least until the tumor stops shrinking. […] If the tumor shrinks enough, surgery might be done if the doctor thinks it can be removed safely. […] The targeted drug imatinib (Gleevec) is typically the preferred first treatment for most advanced GISTs.
#13 The management of metastatic GIST: current standard and investigational therapeutics | Journal of Hematology & Oncology | Full Text
https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-01026-6
Imatinib is a selective, small molecule inhibitor of three receptor tyrosine kinases: the transmembrane receptor KIT, the chimeric BCR-ABL fusion oncoprotein of chronic myeloid leukemia and PDGFRA. In 2002, the FDA approved imatinib for the management of patients with advanced GIST. […] The clinical benefit rate of imatinib was 81%; with 53.7% of patients achieving a RECIST partial response. […] Sunitinib is another small molecule, receptor TKI. It targets KIT/PDGFR, colony stimulating factor 1 receptor (CSF1R), Fms-related tyrosine kinase 3, RET and has anti-angiogenic activity by inhibiting vascular endothelial growth factor receptors (VEGFR1-3). […] Regorafenib is another oral multi-targeted kinase inhibitor that targets a number of pathways involved in tumor growth including tumor angiogenesis (VEGFR-1, -2, and -3, and TIE2), oncogenesis (KIT, RET, RAF-1, BRAF and BRAFV600E), and the tumor microenvironment [PDGFR and fibroblast growth factor receptor (FGFR)].
#14 Gastrointestinal Stromal Tumors Treatment (PDQÂ®) – NCI
https://www.cancer.gov/types/soft-tissue-sarcoma/hp/gist-treatment-pdq
There is universal agreement that standard chemotherapy has no role in the primary therapy of GISTs. […] Neoadjuvant imatinib may be used for patients with very large primary GISTs or poorly positioned small GISTs until surgical therapy is feasible. […] The primary treatment of patients with metastatic or recurrent GISTs involves medical therapy with a TKI. […] Therapy with imatinib is the standard first-line treatment for most patients with metastatic or recurrent disease. […] In the case of tumor progression (or intolerance to imatinib), data support second-line therapy with either imatinib dose escalation to 800 mg per day or sunitinib. […] The FDA has approved regorafenib for the treatment of GISTs that are refractory to first-line therapy. […] Ripretinib is indicated for patients with advanced GISTs who have disease progression on (or are intolerant to) three or more TKIs, including imatinib. […] Overall, the indications for surgery in the management of metastatic or recurrent GISTs include: Stable disease, Limited disease progression, Oncological emergencies including hemorrhage, perforation, obstruction, or abscess.
#15 Gastrointestinal Stromal Tumors (GISTs) Treatment & Management: Approach Considerations, Medical Care, Surgical Care
https://emedicine.medscape.com/article/278845-treatment
When feasible, surgical resection is the treatment of choice for gastrointestinal stromal tumors (GISTs) and offers the only chance for cure. Medical therapy is indicated in the following four scenarios: […] Medical therapy consists of tyrosine kinase inhibitors (TKI), with the most commonly recommended first-line agent being imatinib mesylate (Gleevec). […] Imatinib is the standard choice for adjuvant therapy of GISTs, as well as for treatment of locally advanced inoperable and metastatic GISTs, but GISTs vary in their response to imatinib. […] The use of imatinib can be guided by genotyping of KIT and PDGFRA mutations. […] Imatinib shows the highest activity in GISTs that contain the mutation in exon 11 of KIT; approximately 90% of those patients respond. […] Most GISTs with PDGFRA gene mutations respond to imatinib, with the notable exception of those with D842V.
#16 Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines | British Journal of Cancer
https://www.nature.com/articles/s41416-024-02672-0
When R0 resection is considered difficult to achieve or is thought likely to result in major functional sequelae, e.g. total gastrectomy or abdominoperineal resection of rectum, neo-adjuvant imatinib should be considered provided there is a potentially sensitive mutation. […] Adjuvant treatment with imatinib for 3 years was associated with improved relapse-free and overall survival compared with 1 year of therapy in a randomised trial in high-risk patients. […] In patients with inoperable and metastatic disease, imatinib is the standard treatment, including patients who had previously received the drug as adjuvant therapy without relapse during this treatment. […] The standard dose of imatinib is 400mg daily. However, data have shown that patients with KIT exon 9 variants fare better in terms of progression-free survival (PFS) on a higher dose of 800mg daily, which is therefore the standard treatment in this subgroup.
#17 Systemic Treatment for Gastrointestinal Stromal TumorâA State of Art – touchONCOLOGY
https://touchoncology.com/gastrointestinal-cancers/journal-articles/systemic-treatment-for-gastrointestinal-stromal-tumor-a-state-of-art/
Although significant gains have been made in the treatment of GIST patients, future research is still warranted to help further improve clinical outcomes of patients with GIST. […] Level 1 evidence supports the use of imatinib as first-line treatment for advanced/metastatic GIST based on its high clinical benefit rate of 80 %, median progression-free survival (mPFS) approaching 24 months, and a median overall survival (mOS) of nearly 5 years based on extended follow-up of the initial pivotal B2222 phase II trial. […] Imatinib should be continued indefinitely in nonprogressing tolerant patients with metastatic disease. […] The importance of continuous imatinib therapy in advanced GIST patients was demonstrated from the long-term follow-up results of the phase II B2222 study and updated results of the BFR14 trial.
#18 The management of metastatic GIST: current standard and investigational therapeutics | Journal of Hematology & Oncology | Full Text
https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-01026-6
Imatinib is a selective, small molecule inhibitor of three receptor tyrosine kinases: the transmembrane receptor KIT, the chimeric BCR-ABL fusion oncoprotein of chronic myeloid leukemia and PDGFRA. In 2002, the FDA approved imatinib for the management of patients with advanced GIST. […] The clinical benefit rate of imatinib was 81%; with 53.7% of patients achieving a RECIST partial response. […] Sunitinib is another small molecule, receptor TKI. It targets KIT/PDGFR, colony stimulating factor 1 receptor (CSF1R), Fms-related tyrosine kinase 3, RET and has anti-angiogenic activity by inhibiting vascular endothelial growth factor receptors (VEGFR1-3). […] Regorafenib is another oral multi-targeted kinase inhibitor that targets a number of pathways involved in tumor growth including tumor angiogenesis (VEGFR-1, -2, and -3, and TIE2), oncogenesis (KIT, RET, RAF-1, BRAF and BRAFV600E), and the tumor microenvironment [PDGFR and fibroblast growth factor receptor (FGFR)].
#19 Gastrointestinal stromal tumour | Soft tissue sarcoma | Cancer Research UK
https://www.cancerresearchuk.org/about-cancer/soft-tissue-sarcoma/types/gastrointestinal-stromal-tumour
You might have imatinib to treat a GIST that cant be completely removed with surgery, or which has spread before surgery. […] Your doctor might recommend that you have sunitinib (Sutent) in one of the following situations: imatinib has stopped working or you have had severe side effects with imatinib treatment. […] Regorafenib (Stivarga) is used to treat advanced GIST. Your doctor might recommend regorafenib if you have had treatment with imatinib and sunitinib and these drugs have not worked or caused bad side effects.
#20 Gastrointestinal Stromal Tumors (GISTs) Treatment & Management: Approach Considerations, Medical Care, Surgical Care
https://emedicine.medscape.com/article/278845-treatment
There is consensus that patients whose GISTs have the PDGFRA D842V mutation should not be treated with any adjuvant therapy, given the lack of sensitivity of this genotype; however, neoadjuvant avapritinib may be considered in such patients if R0 surgery is not feasible or is likely to result in major sequelae. […] GISTs with mutations in the succinate dehydrogenase (SDH) gene that result in deficiency of SDH are also generally resistant to TKI therapy, although theoretically these tumors may have greater sensitivity to TKIs with a prominent antiangiogenic mechanism of action (eg, sunitinib, regorafenib). […] Surgical resection is the mainstay of treatment for localized tumors in these patients, but recurrence is common. […] Imatinib comes in 100-mg tablets and can thus be given in graduated doses (100, 200, 300, 400, 500, 600, 700, 800 mg) while monitoring treatment responses.
#21 The management of metastatic GIST: current standard and investigational therapeutics | Journal of Hematology & Oncology | Full Text
https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-01026-6
Ripretinib is a potent switch pocket control inhibitor of KIT and PDGFR kinases and has activity against a broad range of mutations. […] Avapritinib is a potent, highly selective oral inhibitor of PDGFR mutant kinases. […] The recommended phase II dose was determined to be 300 mg once daily and the FDA approved avapritinib in January 2020 for adults with inoperable GIST harboring a PDGFRA exon 18 mutations, including the D842V mutation. […] In the absence of an appropriate clinical trial, other therapeutic options include (1) an alternative TKI (off-label use), (2) re-challenge with imatinib or other TKI (3) the addition of an mTOR inhibitor to imatinib or sorafenib.
#22 Current treatment strategies and future perspectives for gastrointestinal stromal tumors
https://pmc.ncbi.nlm.nih.gov/articles/PMC8788163/
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate from the gastrointestinal tract, mostly from the stomach. […] Surgery is the first line of treatment, and if the tumor is relatively small, minimally invasive surgery such as laparoscopy is performed. […] In recent years, neoadjuvant therapy has been administered to patients with GISTs that are suspected of having a large size or infiltration to other organs. […] Postoperative adjuvant imatinib is the standard therapy for high-risk GISTs. […] The standard treatment for GISTs is radical resection; for tumors classified as high-risk, the standard treatment includes the administration of adjuvant imatinib for at least 3 years post-surgery. […] For adjuvant therapy, the risk of GIST recurrence has been stratified by assessing the mitotic index, tumor size, and tumor location.
#23
https://link.springer.com/article/10.1007/s11864-022-00996-8
Imatinib, sunitinib, regorafenib, and ripretinib are approved in advanced GIST and imatinib is approved for high-risk GIST as adjuvant treatment. […] For patients with symptomatic and/or rapidly progressive disease harboring a PDGFRA exon 18 D842V mutation, avapritinib has been suggested over either imatinib or observation in the setting of initial therapy. […] The primary goal of preoperative imatinib is to reduce tumor size, maximize resectability, and improve quality of life due to avoidance of multi-visceral resection. […] Although surgical resection is the curative treatment for localized GIST, surgery alone can not prevent relapse in patients with high-risk features. The role of adjuvant imatinib (400mg daily) for 1 year was confirmed in the phase III trial (ACOSOG Z9001). Risk of recurrence was substantially reduced by 40% (hazard ratio [HR], 0.6; 95% CI, 0.43 to 0.75; adjusted p 0.001) in imatinib arm.
#24 Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines | British Journal of Cancer
https://www.nature.com/articles/s41416-024-02672-0
When R0 resection is considered difficult to achieve or is thought likely to result in major functional sequelae, e.g. total gastrectomy or abdominoperineal resection of rectum, neo-adjuvant imatinib should be considered provided there is a potentially sensitive mutation. […] Adjuvant treatment with imatinib for 3 years was associated with improved relapse-free and overall survival compared with 1 year of therapy in a randomised trial in high-risk patients. […] In patients with inoperable and metastatic disease, imatinib is the standard treatment, including patients who had previously received the drug as adjuvant therapy without relapse during this treatment. […] The standard dose of imatinib is 400mg daily. However, data have shown that patients with KIT exon 9 variants fare better in terms of progression-free survival (PFS) on a higher dose of 800mg daily, which is therefore the standard treatment in this subgroup.
#25 Current treatment strategies and future perspectives for gastrointestinal stromal tumors
https://pmc.ncbi.nlm.nih.gov/articles/PMC8788163/
Preoperative treatment with imatinib is therefore attempted in such cases, as tumor shrinkage is essential for ensuring a negative surgical margin and avoiding the risk of rupture from subsequent surgical procedures. […] The contribution of preoperative imatinib therapy varies depending on the location of the tumor and is considered particularly effective in the esophagogastric junction, duodenum, and rectum. […] In GIST classified as high-risk after curative surgery, adjuvant imatinib therapy is standard treatment; the recommended period of therapy is at least 3 years. […] The treatment of unresectable, advanced, and recurrent GISTs is mainly based on TKI administration; however, surgical intervention may be possible in some cases. […] If the response to imatinib is good and the disease is controlled, surgery may be indicated.
#26 Systemic Treatment for Gastrointestinal Stromal TumorâA State of Art – touchONCOLOGY
https://touchoncology.com/gastrointestinal-cancers/journal-articles/systemic-treatment-for-gastrointestinal-stromal-tumor-a-state-of-art/
The significant RFS benefit of adjuvant imatinib has also been shown in multiple prospective studies in China, Japan, Korea, and Europe. […] The role of adjuvant therapy in GIST is slowly becoming better defined, as there are now two phase III studies (North America and Europe) to support the use of adjuvant therapy in surgically R0/R1 resected GIST. […] Neoadjuvant therapy is generally viewed as a reasonable option for tumor downstaging, and helps reduce short- and long-term surgical morbidities, resulting in organ preservation/function, and achieve microscopic R0 resection for marginally operable GIST tumors. […] The safety and efficacy of neoadjuvant imatinib has been established in several prospective and retrospective studies. […] Currently there are no approved systemic treatments after imatinib, imatinib dose escalation, sunitinib, regorafenib, and rechallenging with imatinib. […] Systemic treatments for GIST have advanced dramatically over a relatively short time period.
#27 Gastrointestinal Stromal Tumors (GIST) > Fact Sheets > Yale Medicine
https://www.yalemedicine.org/conditions/gastrointestinal-stromal-tumors-gist
Treatments include surgery, targeted therapy, ablation, embolization, radiation therapy […] Fortunately, several types of treatment are available for GISTs. These include surgery, which can cure the disease in some cases, and targeted therapies, which can help reduce or delay the recurrence of the cancer. […] Treatment for GISTs includes: Monitoring. For some tumors less than 2 cm in size that are at low risk of spreading, doctors may recommend monitoring with EUS every 6 to 12 months. Surgery. Surgical removal of the tumor is the primary treatment for GISTs that have not spread to other parts of the body. In some cases, surgery is performed to remove primary and metastatic tumors. Small tumors may be removed using a minimally invasive surgical procedure known as laparoscopy. In some cases, surgery can be curative. Targeted therapy. This treatment uses drugs designed to target specific components of cancer cells that are not found in healthy cells. GISTs are treated with targeted drugs called tyrosine kinase inhibitors (TKIs). Several types of TKIs are available, including imatinib, sunitinib, regorafenib, and avapritinib, among others. Targeted therapy may be used before surgery to shrink the tumor or after surgery to destroy any cancer cells that remain. It is also used in cases in which cancer has spread to other parts of the body. Ablation and embolization. These treatments may be used in cases in which the cancer has spread to the liver, and if surgery is not an option. In ablation, chemicals, heat, cold, microwaves, or high energy radio waves are used to destroy cancer cells. In embolization, a doctor injects substances into blood vessels with the aim of starving cancer cells in the liver of a blood supply. Radiation therapy. Though radiation therapy is not usually used to treat GISTs, it may be used as part of palliative care to reduce pain.
#28 Gastrointestinal stromal tumors: a comprehensive review – Parab – Journal of Gastrointestinal Oncology
https://jgo.amegroups.org/article/view/23883/19709
GISTs that are CD117 and PDGFRA positive are thought to benefit from this therapy. […] Sunitinib treatment is the preferred therapy for exon 9 mutations and wild-type GISTs. […] Patients with exon 13 or 14 mutations benefit from sunitinib and exon 17 mutations benefit from ponatinib. […] In addition to surgery and targeted therapy, it is important that patients who fall into the high-risk categories for metastasis follow-up with serial CT scans every three months for five years. […] If a patient cannot undergo surgical resection, then CT guided radiofrequency ablation (RF) may be an option. […] Metastatic GISTs are developing resistance to imatinib and sunitinib. […] The results of the study showed that regorafenib at a standard dosage of 160 mg daily can decrease metastasis and the size of tumors in highly refractory populations. […] Ponatinib has activity against BCR-ABL, CD117, and PDGFRA. […] Nivolumab can be used alone or in combination with ipilimumab, a CTLA4 blocker. […] EUS alcohol ablation for GISTs requires further research, but may be an effective treatment when surgery is contraindicated due to comorbidities.
#29 Treatments for GIST
https://www.gistsupport.org/treatments/
Hepatic artery embolization is a surgical procedure for treatment of liver metastases of GIST. […] Radiofrequency ablation is a surgical procedure for treatment of liver metastases of GIST. […] Drugs approved for other diseases that may be prescribed for GIST at a physicians discretion. […] the Bad Nauheim Declaration, endorsed by GIST Support International, for the right of all GIST cancer patients to receive up-to-date treatment.
#30 Gastrointestinal Stromal Tumors Treatment – NCI
https://www.cancer.gov/types/soft-tissue-sarcoma/patient/gist-treatment-pdq
Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change. […] If a GIST gets worse during treatment or there are side effects, supportive care is usually given. […] Treatment of GISTs that are metastatic (spread to other parts of the body) or recurrent (came back after treatment) may include targeted therapy with imatinib mesylate. […] Many GISTs treated with a tyrosine kinase inhibitor (TKI) become refractory (stop responding) to the drug after a while.
#31 Gastrointestinal Stromal Tumors | Conditions & Treatments | UCSF Health
https://www.ucsfhealth.org/conditions/gastrointestinal-stromal-tumor
UCSF’s highly trained and experienced GI oncologists and surgeons offer advanced, effective care for gastrointestinal stromal tumors. They provide each patient with a precise diagnosis and a personalized treatment plan, which may include surgery, medications or both. […] The right initial treatment for a gastrointestinal stromal tumor depends on whether it can be surgically removed and whether it has spread within the body. Later on, treatment options may be different if the cancer doesnt respond to treatment or responds but then comes back. […] Very small GISTs (smaller than the eraser on a pencil tip) sometimes remain as they are neither growing larger nor spreading. In these cases, doctors may recommend a watch-and-wait approach, where the tumor is checked regularly for signs of growth.
#32 logo–sylvester
https://umiamihealth.org/en/sylvester-comprehensive-cancer-center/treatments-and-services/bone-and-soft-tissue-sarcoma/soft-tissue-sarcomas/gastrointestinal-stromal-tumors
Active Surveillance (Watchful Waiting): Sometimes your doctor may recommend waiting on treatment. This is called active surveillance, or watchful waiting. If we believe it is best to wait for more signs or symptoms before treating a GIST, we will continue monitoring your condition through regularly scheduled testing. […] Supportive Care: Supportive care may be offered if your tumor gets worse or if you have additional side effects of the tumor or your treatment. It can include pain management, psychological, social, and spiritual support. The goal is to help improve the quality of life for patients who have a serious or life-threatening disease. […] Clinical Trials: If your doctor believes you would benefit from enrollment in a clinical trial, he or she will discuss that option with you. Clinical trials are investigative studies of the newest available drugs, drug combinations or surgical approaches to treat a specific tumor.
#33 Gastrointestinal Stromal Tumors
https://www.texasoncology.com/types-of-cancer/gastrointestinal-stromal-tumors
Stivarga is a multi-kinase inhibitor that targets multiple biological pathways involved in GIST development. […] Standard chemotherapy is not effective for treating GIST and should not be used. […] The purpose of precision cancer medicine is to define the genomic alterations in the GIST DNA that is driving growth of the cancer. […] There are several precision cancer medicines that have been recently approved for treatment and others are in development.
#34 GIST (Gastrointestinal Stromal Tumor) | Memorial Sloan Kettering Cancer Center
https://www.mskcc.org/cancer-care/types/soft-tissue-sarcoma/types/gist-gastrointestinal-stromal-tumor
A gastrointestinal stromal tumor (GIST) is a rare cancer. It is a type of soft tissue sarcoma that often begins in the abdomen. […] The primary treatment for a GIST is surgery to remove the tumor. The surgery thats right for you depends on the exact size and location of the tumor. […] Surgery for a GIST is often followed by a three-year course of the drug imatinib (Gleevec). Some people dont need any treatment other than surgery. Radiation is rarely recommended for a GIST. […] For GISTs that come back after initial treatment, the soft tissue sarcoma experts at MSK may be able to offer surgery, cryoablation, radiofrequency ablation, or imatinib or other drug therapies, such as sunitinib (Sutent).
#35 Gastrointestinal Stromal Tumors (GIST): Staging and Treatment | OncoLink
https://www.oncolink.org/cancers/sarcomas/sarcoma-soft-tissue/gastrointestinal-stromal-tumors-gist-staging-and-treatment
The primary targeted therapy used in the treatment of GIST is imatinib. Imatinib targets KIT and PDGFRA proteins. This medication can be used before surgery or after surgery, usually for 1-3 years depending on tumor size and location. […] Procedures called ablation and embolization may be used if the GIST has spread to the liver. […] Radiation is the use of high-energy x-rays to kill cancer cells. Radiation therapy is not often used in the treatment of GIST. However, it may be used to manage symptoms, such as pain from metastatic cancer. […] You may be offered a clinical trial as part of your treatment plan.
#36 Treating Gastrointestinal Stromal Tumors | American Cancer Society
https://www.cancer.org/cancer/types/gastrointestinal-stromal-tumor/treating.html
It’s important to discuss all treatment options, including their goals and possible side effects, with your doctors to help make the decision that best fits your needs. […] Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the-art cancer treatment. […] You may hear about alternative or complementary methods to relieve symptoms or treat your cancer that your doctors havent mentioned. […] Be sure to talk to your cancer care team about any method you are thinking about using. They can help you learn what is known (or not known) about the method, which can help you make an informed decision. […] Whether you are thinking about treatment, getting treatment, or not being treated at all, you can still get supportive care to help with pain or other symptoms.
#37 Gastrointestinal Stromal Tumors (GIST) Cancer
https://www.cancercenter.com/cancer-types/soft-tissue-sarcoma/types/gastrointestinal-stromal-tumors
A treatment plan depends on the characteristics of the cancer, as well as the patients age, personal preference and overall physical health. The basic treatment options for a GIST include: […] Surgery is the most common GIST treatment. […] Targeted therapyThese drugs are the main treatment for an unresectable, recurrent or metastatic GIST. […] Unlike other GI cancers, chemotherapy and radiation therapy arent usually recommended for treating GISTs. Targeted treatment and other new treatments are typically done as part of a clinical trial. Patients should ask whether clinical trials are the right approach for them.
#38 Promising Research to Advance Treatment of Gastrointestinal Stromal Tumors
https://www.targetedonc.com/view/promising-research-to-advance-treatment-of-gastrointestinal-stromal-tumors
Considering this, the trial is moving on to the phase 3 component comparing the 2-drug regimen vs sunitinib alone. […] These patients may benefit from the synergistic effect of targeting not only the primary driver mutations, but also the second mutations. […] One exciting trial came out in 2022, which is a phase 2, single arm trial of imatinib along with a MEK inhibitor called binimetinib [Mektovi], and this one recruited 42 patients with metastatic GIST. […] Imatinib and binimetinib showed a 69% partial response [PR] rate, along with a median PFS of about 30 months with median overall survival was not reached. […] The other things that I think is promising is looking at combination of TKI and immunotherapy. […] The primary outcome for that trial is PFS, and that should read out sometime in 2026. […] I’m optimistic that looking at different TKIs will help give us additional options, but I think, in the future, combination options are going to be what ultimately changes standard of care.
#39 Promising Research to Advance Treatment of Gastrointestinal Stromal Tumors
https://www.targetedonc.com/view/promising-research-to-advance-treatment-of-gastrointestinal-stromal-tumors
Targeted therapy for gastrointestinal stromal tumors (GIST) has offered prolonged survival and better disease control compared with historic treatments. […] Currently, both early-phase and late-phase clinical trials of immunotherapy added to targeted therapy have shown encouraging results. […] We need to find first-line options that essentially keep patients alive with better disease control for longer. […] I’m optimistic that looking at different TKIs [tyrosine kinase inhibitors] will help give us additional options, but I think, in the future, combination options are going to be what ultimately changes standard of care. […] The goal of the PEAK trial is to assess whether this novel agent will add to benefit. […] Bezuclastinib targets these mutations in exon 17 and 18. […] In this early trial with early follow-up, there was excellent disease control across the cohort.
#40
https://journals.lww.com/otm/fulltext/2024/06000/systemic_therapy_in_gastrointestinal_stromal.3.aspx
The advent of targeted therapy has revolutionized the prognosis of patients with advanced GISTs; however, the emergence of drug resistance remains a significant challenge that warrants further investigation. […] The approval of imatinib for the treatment of advanced GISTs marked the beginning of a new era of targeted oncological treatments. […] Sunitinib has been approved for use in second-line settings in patients experiencing disease progression or those who cannot tolerate imatinib. […] For patients who do not respond to either imatinib or sunitinib, regorafenib and ripretinib have been approved as third- and fourth-line therapies, respectively. […] Despite these advances, resistance to imatinib, sunitinib, regorafenib, and ripretinib remains challenging in clinical practice. […] Immunotherapy has shown potential as a novel treatment for patients with advanced GISTs.
#41 Systemic Treatment for Gastrointestinal Stromal TumorâA State of Art – touchONCOLOGY
https://touchoncology.com/gastrointestinal-cancers/journal-articles/systemic-treatment-for-gastrointestinal-stromal-tumor-a-state-of-art/
The availability of the tyrosine kinase inhibitor (TKI) small molecule imatinib has revolutionized the systemic treatment for gastrointestinal stromal tumor (GIST), historically one of the most chemoresistant solid malignancies. […] Imatinib is now accepted as the first-line systemic treatment for advanced GIST and subsequently has become the standard systemic treatment for GIST in the neoadjuvant and adjuvant settings. […] Sunitinib and regorafenib have been approved for second- and third-line treatments, respectively, for patients with advanced GIST progressing on imatinib. […] The dramatic and continuing efficacy of TKIs targeting oncogenic driver pathways such as KIT, platelet-derived growth factor receptor alpha (PDGFR), and vascular epithelial growth factor receptors (VEGFs), in advanced GIST supports the utility of targeted therapy in oncogene addicted solid malignancies.
#42 Innovative Research Continues to Propel Individualized GIST Treatments
https://www.onclive.com/view/innovative-research-continues-to-propel-individualized-gist-treatments
Beyond this, the National Comprehensive Cancer Network Guidelines have also incorporated ripretinib as an option to consider for patients who are intolerant to sunitinib in the second-line setting. This [recommendation] is based on the INTRIGUE data. […] The standard methodology used to molecularly characterize GIST remains tumor tissue sequencing. […] The phase 1 study is underway, and we are looking forward to seeing the data from this as a novel combination therapeutic approach to treating patients with advanced GIST. […] GIST is a rare cancer. It is important that patients are given the opportunity to meet a sarcoma specialist, because that may offer them the potential for clinical trials that are ongoing in this setting, that they may not otherwise be aware of.
#43 Current treatment strategies and future perspectives for gastrointestinal stromal tumors
https://pmc.ncbi.nlm.nih.gov/articles/PMC8788163/
The results of cytoreductive surgery for GIST with local progression during regorafenib treatment in the third line have also been reported. […] Imatinib is administered as adjuvant therapy for the high-risk group after surgery, as GISTs generally harbor an imatinib-sensitive mutation. […] The most frequent KIT exon 11 mutations are sensitive to imatinib, whereas the PDGFRA exon 18 D842 V-mutation is considered to be imatinib-resistant. […] These results suggest that genetic mutations have prognostic value and that grouping by mutation is useful in determining the indications of adjuvant therapy; it also complements clinicopathological risk stratification.
#44 Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines | British Journal of Cancer
https://www.nature.com/articles/s41416-024-02672-0
Gastrointestinal stromal tumours (GIST) are rare cancers, with an estimated unadjusted incidence of 1.5/100,000/year. […] Treatment of GIST depends on the size and location of the tumour, the age and co-morbidity of the patient and the presence or absence of symptoms or complications such as perforation, bleeding or obstruction. Multidisciplinary treatment planning is essential. This should involve histopathologists, radiologists, surgeons and medical oncologists, as well as gastroenterologists and nuclear medicine specialists as applicable. Such teams are available in reference centres for sarcomas and GISTs, which treat a large number of GIST patients annually. […] For a histologically proven GIST of 2cm or greater, the standard treatment is excision in patients that are fit. […] Standard treatment of localised GIST is complete surgical excision of the lesion, with no dissection of clinically negative lymph nodes. Surgery should be performed by a subspecialty surgeon who is fully trained and experienced in radical anatomic site-specific cancer surgery linked to a specialist sarcoma centre, with the aim of achieving an R0 resection.
#45 Treatment of Gastrointestinal Stromal Tumors (GISTs): A Focus on Younger Patients
https://www.mdpi.com/2072-6694/14/12/2831
For adult patients with unresectable or metastatic GIST harboring the PDGFRA D842V mutation, which is resistant to imatinib, avapritinib has been approved for first-line therapy based on phase I NAVIGATOR study results. […] Patients who progress or are intolerant to imatinib may be treated with sunitinib in the second-line therapy. […] Regorafenib is another oral inhibitor that potently blocks multiple protein kinases, including kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF, BRAFV600E), metastasis (VEGFR3, PDGFR, FGFR), and tumor immunity (CSF1R). […] For patients with GISTs with mutations resistant to imatinib, sunitinib, regorafenib, ripretinib, and avapritinib, referral to a clinical trial is recommended. […] The treatment strategy should be defined and implemented by the multidisciplinary team in the sites experienced in sarcomas. Molecular testing should be done whenever possible, as the molecular profile may differ from patients above 40 and may influence the choice of systemic therapy.
#46 Typical Treatment Options for Gastrointestinal Stromal Tumors | American Cancer Society
https://www.cancer.org/cancer/types/gastrointestinal-stromal-tumor/treating/by-spread.html
If imatinib is used, it is continued for as long as the tumor doesn’t grow (and the side effects are tolerable). […] If the cancer comes back (recurs) in or near the place it started, it is called a local recurrence. […] For most recurrences, treatment with the targeted drug imatinib (Gleevec) is often the first option to try to shrink any tumors, as long as it is still effective and the patient can tolerate taking it. […] If the targeted drugs mentioned above are no longer helpful, some doctors may recommend trying other targeted drugs, such as sorafenib (Nexavar), dasatinib (Sprycel), nilotinib (Tasigna), or pazopanib (Votrient), although it’s not yet clear how helpful these drugs are.
#47 Gastrointestinal stromal tumour | Macmillan Cancer Support
https://www.macmillan.org.uk/cancer-information-and-support/soft-tissue-sarcoma/gastrointestinal-stromal-tumour
Imatinib is a TKI drug given: […] If the GIST is bigger than 2cm, you may have surgery to remove it. You may have targeted therapy before surgery to shrink the tumour. If the GIST is found to be high-risk, you usually have targeted therapy after surgery. […] Surgery may also be used to treat GISTs that come back after treatment. […] If a GIST comes back after treatment it may come back where it first started. This is called a local recurrence. Or it may come back in another part of the body which is called secondary or metastatic cancer. […] GIST that comes back is usually treated with targeted therapy. Surgery may also be an option if there is only 1 small new GIST. Your doctor or specialist nurse will talk to you about your treatment options.
#48 Gastrointestinal Stromal Tumors | Nebraska Hematology Oncology – Cancer Care Treatment Blood Disorders Clinical Trials Lincoln Nebraska (NE)
https://www.yourcancercare.com/types-of-cancer/gastrointestinal-stromal-tumors
Stivarga (regorafenib): Stivarga is a multi-kinase inhibitor that targets multiple biological pathways involved in GIST development. […] Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells and is only rarely used in for the treatment of GIST. […] Chemotherapy is the use of drugs to destroy cancer cells, usually by ending the cancer cells ability to grow and divide. However, standard chemotherapy is not effective for treating GIST and should not be used. […] When a recurrence occurs, a new cycle of genomic testing is required to learn as much as possible about the recurrence. […] The purpose of precision cancer medicine is to define the genomic alterations in the GIST DNA that is driving growth of the cancer. […] There are several precision cancer medicines that have been recently approved for treatment and others are in development.
#48 Gastrointestinal Stromal Tumors | Nebraska Hematology Oncology – Cancer Care Treatment Blood Disorders Clinical Trials Lincoln Nebraska (NE)
https://www.yourcancercare.com/types-of-cancer/gastrointestinal-stromal-tumors
Gastrointestinal stromal tumors (GIST) are a relatively rare but aggressive type of soft-tissue sarcoma. […] Tyrosine kinase inhibitors (TKI) are precision cancer medicines that blocks tyrosine kinase activity slowing the growth of the cancer. TKIs are currently the main medical treatment for GIST. […] Complete surgical removal of localized tumors appears to prolong survival and standard chemotherapy and radiation are rarely used. Patients should consider participation in a clinical trial utilizing new, innovative therapies also provides promising treatment. […] Surgery may be used as initial therapy to completely remove GIST and to remove metastatic tumors. […] For patients with localized GIST, surgery is the standard treatment and should be performed whenever possible. […] The goal of surgery is complete removal of the tumor with an intact pseudocapsule and negative microscopic margins.
#49 Daily Life With GIST
https://www.webmd.com/cancer/daily-life-with-gist
Gastrointestinal stromal tumor is a type of cancer known as a soft tissue sarcoma that affects the GI tract. However, GIST has become a treatable disease over time. Maintaining a healthy lifestyle and following doctors orders will help improve your treatment experience. […] GIST treatment may have side effects as well. Talk to your doctor if symptoms or treatment side effects persist or become severe or when symptoms interfere with your life. Talk to your health care provider about any treatment side effects so that your doctor can prescribe supportive medication to help relieve treatment-related symptoms. […] After surgery, vitamin and mineral deficiencies may develop due to a lack of absorption. Therefore, supplements may be helpful. Talk to your doctor about which supplements may be helpful for you. […] Plan a work schedule around GIST. Work flexible hours and take breaks. If possible, take a leave of absence from work. Under the Family and Medical Leave Act, there may be eligibility for up to 12 weeks of leave because of the illness.
#50 Treating Gastrointestinal Stromal Tumors | American Cancer Society
https://www.cancer.org/cancer/types/gastrointestinal-stromal-tumor/treating.html
For some people, when treatments have been tried and are no longer controlling the cancer, it could be time to weigh the benefits and risks of continuing to try new treatments. […] Remember that even if you choose not to treat the cancer, you can still get supportive care to help with pain or other symptoms.
#51 GIST Treatments and Side Effects
https://www.webmd.com/cancer/gist-manage-effects
Ripretinib, approved in May 2020, is used to treat advanced GISTs if three or more TKIs including imatinib arent able to be used or no longer work. […] In addition to standard care, people with advanced GIST may be able to sign up for clinical trials testing new treatments. […] And remember: Get palliative care to help relieve troublesome symptoms of GIST and side effects and improve your quality of life while getting your treatment.
#52 Treatment of Gastrointestinal Stromal Tumors (GISTs): A Focus on Younger Patients
https://www.mdpi.com/2072-6694/14/12/2831
For GISTs insensitive to imatinib, i.e., GISTs with PDGFRA exon 18 mutations (including the D842V mutation), neoadjuvant avapritinib may be considered. […] The available data indicate that perioperative imatinib should be used for three years (including preoperative therapy). […] The ESMO guidelines recommend adjuvant therapy for high-risk patients, and for patients with intermediate risk, the decision should be individualized, and the decision-making process may include genotyping for KIT mutations. […] In unresectable and metastatic settings, systemic therapy with targeted therapies is the mainstay of disease management. GISTs are generally resistant to chemotherapy and radiation therapy. […] Imatinib is the standard of care in the first line of unresectable and metastatic GISTs. It was the first drug introduced into clinical practice in GISTs.
#53 Treatment of Gastrointestinal Stromal Tumors (GISTs): A Focus on Younger Patients
https://www.mdpi.com/2072-6694/14/12/2831
For adult patients with unresectable or metastatic GIST harboring the PDGFRA D842V mutation, which is resistant to imatinib, avapritinib has been approved for first-line therapy based on phase I NAVIGATOR study results. […] Patients who progress or are intolerant to imatinib may be treated with sunitinib in the second-line therapy. […] Regorafenib is another oral inhibitor that potently blocks multiple protein kinases, including kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF, BRAFV600E), metastasis (VEGFR3, PDGFR, FGFR), and tumor immunity (CSF1R). […] For patients with GISTs with mutations resistant to imatinib, sunitinib, regorafenib, ripretinib, and avapritinib, referral to a clinical trial is recommended. […] The treatment strategy should be defined and implemented by the multidisciplinary team in the sites experienced in sarcomas. Molecular testing should be done whenever possible, as the molecular profile may differ from patients above 40 and may influence the choice of systemic therapy.
#54 Ripretinib in the treatment of patients with advanced gastrointestinal stromal tumors (GIST) | Babula | Oncology in Clinical Practice
https://journals.viamedica.pl/oncology_in_clinical_practice/article/view/96771
According to the latest Polish and international guidelines, ripretinib is the preferred option for fourth-line treatment in patients with inoperable, progressive, or metastatic GIST after treatment with imatinib, sunitinib, and regorafenib at a dose of 150 mg/day. […] Further clinical trials are needed to confirm the efficacy of ripretinib in the treatment of GIST with PDGFRA D842V mutations.