Paraganglioma – Rokowania, prognozy i postęp choroby

Paraganglioma
Rokowania, prognozy i postęp choroby

Paraganglioma, jako rzadki guz neuroendokrynny, charakteryzuje się zmiennym potencjałem przerzutowym i nieprzewidywalnym przebiegiem klinicznym. Wszystkie guzy typu PPGL według klasyfikacji WHO 2017 mają potencjał przerzutowy, co komplikuje prognozowanie. Pięcioletnie przeżycie w przypadku przerzutowej postaci wynosi poniżej 50%, a mediana całkowitego przeżycia (OS) po leczeniu 177Lu-DOTATATE to 49,6 miesiąca, z medianą przeżycia wolnego od progresji (PFS) 21,6 miesiąca. Czynniki prognostyczne związane z gorszym rokowaniem obejmują m.in. wynik PASS ≥7, Ki-67 ≥15%, ujemny wychwyt MIBG, lokalizację podprzeponową, wielkość guza >5 cm, podwyższone poziomy metoksytyraminy oraz cechy histopatologiczne takie jak inwazja naczyń, martwica typu comedo i wysoki wskaźnik mitotyczny (>3 mitoz/10 HPF). Genetycznie istotne są mutacje SDHB, aktywacja telomerazy i utrata funkcji ATRX, choć rola SDHB w prognozie jest obecnie dyskutowana.

Prognostyczne znaczenie w Paraganglioma

Paraganglioma, należąca do rzadkich guzów neuroendokrynnych, charakteryzuje się zmiennym potencjałem przerzutowym i nieprzewidywalnym przebiegiem klinicznym. Według klasyfikacji WHO z 2017 roku wszystkie guzy typu PPGL (pheochromocytoma i paraganglioma) mają potencjał przerzutowy, odchodząc od tradycyjnego podziału na łagodne i złośliwe formy. Przewidywanie potencjału przerzutowego paraganglioma stanowi istotne wyzwanie kliniczne, ponieważ żaden pojedynczy wskaźnik nie zapewnia 100% przewidywalności, a dostępne systemy prognostyczne wymagają walidacji w badaniach wieloośrodkowych¹².

Wskaźniki przeżycia w Paraganglioma

Dla pacjentów z przerzutową paraganglioma, wskaźniki przeżycia są zróżnicowane. Badania wskazują, że 5-letnie przeżycie w przypadku przerzutowej postaci choroby wynosi poniżej 50%¹. Według nowszych badań, wskaźniki 5-, 10- i 15-letniego przeżycia po diagnozie przerzutów lub nawrotu wynoszą odpowiednio 73,3%, 62,9% i 31,4%². W innym badaniu oceniającym leczenie za pomocą 177Lu-DOTATATE mediana całkowitego przeżycia (OS) wynosiła 49,6 miesiąca (zakres 8,2-139), a mediana przeżycia wolnego od progresji (PFS) 21,6 miesiąca (zakres 6,7-138)³. Pięcioletnie przeżycie po progresji do fazy przerzutowej jest heterogeniczne i waha się od 40% do 77%⁴.

Czynniki związane z gorszą prognozą

Zidentyfikowano liczne czynniki związane z podwyższonym ryzykiem przerzutów i gorszą prognozą w paraganglioma:

Wynik PASS ≥7 (Pheochromocytoma of the Adrenal Gland Scaled Score) – istotnie gorsze rokowanie⁵⁶
Ki-67 ≥15% – związany z krótszym całkowitym przeżyciem (OS) i przeżyciem wolnym od progresji (PFS)⁷
Ujemny wychwyt MIBG w badaniach obrazowych – numerycznie powiązany z gorszym OS⁸
Położenie podprzeponowe guza⁹
Guzy hormonalnie czynne¹⁰
Zaawansowany wiek w momencie diagnozy¹¹¹²
Wielkość guza pierwotnego >5 cm¹³
Podwyższone poziomy metoksytyraminy (metabolit dopaminy)¹⁴

Czynniki histopatologiczne i genetyczne

Cechy histopatologiczne związane ze zwiększonym ryzykiem przerzutów w paraganglioma obejmują:¹⁵¹⁶

Inwazja tkanek miękkich i naczyń krwionośnych
Szczególne wzorce architektoniczne obejmujące hipercelularność i duże zlewające się gniazda komórek
Martwica typu comedo
Wysoki wskaźnik mitotyczny lub wysoki indeks proliferacyjny Ki-67
Inwazja torebki lub tkanki tłuszczowej
Martwica w obrębie guza
Liczba mitoz >3 na 10 pól widzenia (HPF)

Do genetycznych czynników prognostycznych należą:¹⁷¹⁸

Mutacje genu SDHB (chociaż najnowsze badania podważają jego główną rolę prognostyczną w chorobie przerzutowej)
Aktywacja genu telomerazy oraz utrata funkcji wariantów ATRX – związane z gorszym rokowaniem
Deregulacja telomerów zaangażowana w progresję przerzutową PPGL

Systemy predykcyjne w ocenie potencjału przerzutowego

W celu lepszego przewidywania potencjału przerzutowego opracowano kilka systemów predykcyjnych, jednak żaden z nich nie jest doskonały:¹⁹²⁰²¹

System PASS

Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) jest najwcześniejszym systemem oceny. Mimo że jego zdolność przewidywania przerzutów nie jest zadowalająca, wykazuje dobrą zdolność przewidywania guzów nieprzerzutowych, co ma wartość w określonych zastosowaniach klinicznych. Wyniki PASS ≥7 wiążą się z gorszym rokowaniem²²²³.

System GAPP i M-GAPP

Grading system for adrenal pheochromocytoma and paraganglioma (GAPP) oraz jego zmodyfikowana wersja M-GAPP wymagają dalszej walidacji, ponieważ żaden z tych systemów nie ma wiarygodnego wskaźnika dokładności prognostycznej dla guzów przerzutowych²⁴. Zauważono jednak pozytywną korelację między wynikiem GAPP a potencjałem przerzutowym oraz negatywną korelację z okresem wolnym od przerzutów²⁵.

System COPPs

COmposite Pheochromocytoma/paraganglioma Prognostic Score (COPPs), zaproponowany przez Pierre’a w 2019 roku, składa się z trzech cech kliniczno-histopatologicznych (wielkość guza, martwica, inwazja naczyniowa) połączonych z indeksem proliferacji PS100 i inaktywacją SDHB do przewidywania ryzyka przerzutów i przeżycia wolnego od progresji²⁶.

System ASES

ASES wykazał niską czułość 61% i swoistość 80%. Dokładność przewidywania dla nieprzerzutowych PPGL wynosiła 97%, a dla przerzutowych PPGL zaledwie 18%²⁷.

Nomogramy prognostyczne

Opracowano nomogramy do przewidywania 3- i 5-letniego całkowitego przeżycia (OS) i przeżycia specyficznego dla raka (CSS) u pacjentów ze złośliwym PPGL. Niezależnymi czynnikami prognostycznymi dla OS były: wiek, płeć, typ guza, stadium guza i operacja, podczas gdy dla CSS: wiek, stadium guza i operacja. Nomogramy te wykazały dobrą dokładność predykcyjną z indeksami C wynoszącymi odpowiednio 0,747 i 0,742 dla nomogramów OS i CSS²⁸²⁹³⁰.

Strategie terapeutyczne wpływające na rokowanie

Wybór odpowiedniej strategii terapeutycznej ma znaczący wpływ na rokowanie pacjentów z paraganglioma:³¹³²

Interwencja chirurgiczna

Pacjenci, którzy przeszli zabieg chirurgiczny ze względu na zmiany przerzutowe lub nawrotowe, mieli znacznie lepsze rokowanie. Interwencja chirurgiczna jest kluczowym czynnikiem związanym z lepszym rokowaniem i wyższymi wskaźnikami przeżycia³³.

Terapia PRRT

Terapia peptydowymi receptorami (PRRT) z 177Lu-DOTATATE okazała się obiecującą metodą leczenia guzów neuroendokrynnych, w tym paraganglioma. W badaniu retrospektywnym wykazano, że w grupie pacjentów leczonych tą metodą całkowite przeżycie wynosiło 100%, chociaż mediana PFS była zróżnicowana w zależności od typu guza³⁴³⁵.

Czynniki predykcyjne odpowiedzi na PRRT obejmują:³⁶³⁷

Niski Ki-67 (<15%) wiąże się z dłuższym OS i PFS
PRRT jako terapia pierwszego rzutu wiąże się ze zwiększonym OS
Wartość SUVmax ≥21 w badaniu 68Ga-DOTATATE istotnie przewidywała odpowiedź na PRRT

Terapia 177Lu-DOTATATE jest skuteczną i bezpieczną metodą leczenia pacjentów z przerzutową/nieoperacyjną PPGL. Najczęstsze działania niepożądane to nudności, wymioty i utrata masy ciała. U żadnego z pacjentów nie stwierdzono przejściowej ani trwałej nefrotoksyczności³⁸³⁹.

Prognoza długoterminowa

Prognoza długoterminowa dla pacjentów z paraganglioma jest wysoce zmienna i zależy od wielu czynników, takich jak lokalizacja guzów, status genetyczny i inne. W przypadku wczesnego wykrycia, paraganglioma może być skutecznie leczona i kontrolowana w przeważającej większości przypadków⁴⁰.

Wszystkie przypadki paraganglioma mają potencjał do stania się przerzutowymi, co zdarza się w około 15-25% przypadków. Obecnie nie ma leków na złośliwą paraganglioma, jednak istniejące opcje leczenia mogą zredukować guzy i przedłużyć przeżycie. Niektórzy pacjenci żyją przez dziesięciolecia z przerzutową paraganglioma⁴¹.

Leczenie przerzutowej paraganglioma może obejmować chirurgię, terapię MIBG, terapię PRRT (Lutathera), chemioterapię i inne metody⁴².

Przyszłe kierunki badań

Ze względu na złożoność i heterogeniczność paraganglioma, istnieje pilna potrzeba opracowania nowych, wygodnych, wysoce specyficznych i standardowych systemów oceny, które łączą wiele czynników wpływających na prognozę⁴³. Niezbędne są badania międzynarodowe w celu walidacji biomarkerów i opracowania solidnego modelu predykcyjnego dla choroby przerzutowej⁴⁴.

Zrozumienie mikrośrodowiska guza (TME) w paraganglioma może również poprawić zastosowanie ukierunkowanych immunoterapii w chorobie przerzutowej, chociaż ten obszar badań jest wciąż w początkowej fazie i wymaga dalszej eksploracji⁴⁵.

Istotna jest potrzeba prostych i zwalidowanych narzędzi do lepszego określenia agresywności choroby i ustanowienia dostosowanych do pacjenta schematów leczenia i obserwacji⁴⁶.

System prognostyczny	Główne parametry	Zalety	Ograniczenia
PASS (Pheochromocytoma of the Adrenal Gland Scaled Score)	Cechy histologiczne, w tym inwazja naczyniowa, wzorzec wzrostu, nekroza, aktywność mitotyczna	Dobra zdolność przewidywania guzów nieprzerzutowych, pierwsza skala historycznie	Niezadowalająca dokładność w przewidywaniu przerzutów
GAPP (Grading system for adrenal pheochromocytoma and paraganglioma)	Wzorzec histologiczny, indeks Ki-67, aktywność norepinefryny	Korelacja z potencjałem przerzutowym	Niewystarczająca dokładność predykcyjna, wymaga walidacji wieloośrodkowej
M-GAPP (Modified GAPP)	Modyfikacja GAPP z dodatkowymi parametrami	Potencjalnie lepsza dokładność niż GAPP	Brak wiarygodnej dokładności prognostycznej dla guzów przerzutowych
COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score)	Wielkość guza, martwica, inwazja naczyniowa, indeks proliferacji PS100, inaktywacja SDHB	Kompleksowe podejście uwzględniające wiele czynników	Wymaga walidacji zewnętrznej
ASES	Wieloczynnikowy system oceny	Wysoka dokładność dla guzów nieprzerzutowych (97%)	Niska czułość (61%) i niska dokładność dla guzów przerzutowych (18%)
Nomogramy OS i CSS	Wiek, płeć, typ guza, stadium guza, operacja	Dobre wskaźniki predykcyjne (indeksy C: 0,747 i 0,742)	Wymaga walidacji w większych populacjach

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

Materiały źródłowe

#1 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The prediction of PPGLs metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. There is no unified clinical standard to differentiate metastatic from non-metastatic and a highly effective prediction system is of urgent need.
#1 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. Metastasis can occur in months even decades after the initial diagnosis. Thus, a proportion of patients with PPGL was considered as non-metastatic before surgery, while they were identified to have metastasis during follow up. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. […] A precise prediction of metastatic potential would be important. […] Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies.
#2 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. Metastasis can occur in months even decades after the initial diagnosis. Thus, a proportion of patients with PPGL was considered as non-metastatic before surgery, while they were identified to have metastasis during follow up. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. […] A precise prediction of metastatic potential would be important. […] Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies.
#2 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
The 5-, 10-, and 15-year survival rates after metastasis or recurrent diagnosis were 73.3%, 62.9%, and 31.4%, respectively, which is consistent with previous studies. […] Patients who underwent surgery for metastasis or recurrent lesion had a significantly better prognosis. […] Our study adds to this literature by demonstrating that surgery intervention is associated with better outcomes in patients with metastatic or recurrent PPGL. […] In addition, patients with PASS7 for the primary tumor had a significantly worse prognosis. […] Our findings suggest that surgical intervention is a pivotal factor associated with improved prognosis and higher survival rates.
#3 Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE
https://www.mdpi.com/2072-6694/11/7/909
Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE […] Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. […] The median overall survival (OS) was 49.6 (range 8.2â139) months and median progression-free survival (PFS) was 21.6 (range 6.7â138) months. […] Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). [...] High Ki-67 (â¥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.
#4
https://link.springer.com/article/10.1007/s12022-024-09830-3
Pheochromocytomas (PCCs) and paragangliomas (PGLs, together PPGLs) are the most hereditary tumors known. […] The fourth edition of the World Health Organisation (WHO) classification redefined all PPGLs as malignant neoplasms with variable metastatic potential. […] The metastatic rate differs based on histopathology, genetic background, size, and location of the tumor. […] The challenge in predicting metastatic disease lies in the absence of a clear genotype-phenotype correlation among the more than 20 identified genetic driver variants. […] It appears that no single biomarker alone can reliably predict metastatic risk; instead, a combination of these biomarkers may be necessary to develop an effective prediction model for metastatic disease. […] Five-year survival upon metastatic progression is heterogeneous and varies from 40 to 77%.
#5 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Pheochromocytoma and paraganglioma (PPGL) represent a group of rare neuroendocrine tumors known for their potential to metastasize. […] Our primary objectives were to delineate the long-term clinical outcomes and pinpoint key prognostic determinants. […] A salient finding was that surgical interventions targeting metastatic lesions significantly improved prognosis. […] Further analysis revealed that a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) exceeding 7 closely associated with unfavorable outcomes. […] The value of the PASS score as an informative prognostic tool was evident, suggesting its utility in shaping future therapeutic approaches. […] The prognosis and survival rates for these patients are not well-established. […] Our analysis revealed two main findings.
#6 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
The 5-, 10-, and 15-year survival rates after metastasis or recurrent diagnosis were 73.3%, 62.9%, and 31.4%, respectively, which is consistent with previous studies. […] Patients who underwent surgery for metastasis or recurrent lesion had a significantly better prognosis. […] Our study adds to this literature by demonstrating that surgery intervention is associated with better outcomes in patients with metastatic or recurrent PPGL. […] In addition, patients with PASS7 for the primary tumor had a significantly worse prognosis. […] Our findings suggest that surgical intervention is a pivotal factor associated with improved prognosis and higher survival rates.
#7 Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE
https://www.mdpi.com/2072-6694/11/7/909
Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE […] Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. […] The median overall survival (OS) was 49.6 (range 8.2â139) months and median progression-free survival (PFS) was 21.6 (range 6.7â138) months. […] Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). [...] High Ki-67 (â¥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.
#8 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p= 0.13). […] Our results should be further validated in independent and larger cohorts.
#9 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p= 0.13). […] Our results should be further validated in independent and larger cohorts.
#10 Metastatic pheochromocytoma and paraganglioma: a retrospective multicentre analysis on prognostic and predictive factors to chemotherapy – ecancer
https://ecancer.org/en/journal/article/1523-metastatic-pheochromocytoma-and-paraganglioma-a-retrospective-multicentre-analysis-on-prognostic-and-predictive-factors-to-chemotherapy
In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. […] While prognostic and predictive factors in mPPGL remain unknown, our data suggest that negative baseline MIBG uptake, Ki67 10%, infradiaphragmatic location and functional tumours may be associated with inferior OS. […] No variable was significantly prognostic for OS or predictive of DDC1L. Non-significant large numerical differences were observed in DDC1L according to Ki67 (Ki67 10%: median of 13.7 months versus 10%: 1.8 months; p= 0.1) and OS according to MIBG uptake (median of 72.6 for positive uptake versus 42.1 months for negative uptake; p= 0.13). […] Our results should be further validated in independent and larger cohorts.
#11 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma […] Background: Malignant pheochromocytoma and paraganglioma (PPGL) are rare tumors with few prognostic tools. This study aimed to construct nomograms for predicting 3- and 5-year survival for patients with malignant PPGL. […] Results: Age, gender, tumor type, tumor stage, or surgery were independent prognostic factors for OS in patients with malignant PPGL, while age, tumor stage, or surgery were independent prognostic factors for CSS (P <.05). Based on these factors, we successfully constructed the OS and CSS nomograms. The C-indexes were 0.747 and 0.742 for the OS and CSS nomograms, respectively. In addition, both the calibration curves and ROC curves for the model exhibited reliable performance.
#12 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
Conclusion: We successfully constructed nomograms for predicting the OS and CSS of patients with malignant PPGL. The nomograms could inform personalized clinical management of the patients. […] The prominent risk factors determined by the multivariate analysis were applied to construct nomograms that could predict the 3- and 5-year OS and CSS for PPGL. The nomogram used for OS prediction showed that prognosis was mainly affected by the tumor stage followed by age, tumor type, surgery and gender. Similarly, the nomogram for CSS indicated that tumor stage was also the most significant factor affecting prognosis, followed by age and surgery. […] Our study found that PPGL was highly diverse in the clinical course. Compared with the PHEO or PGL, Extra-PGL showed better OS, but moderate CSS.
#13 Paraganglioma Symptoms, Treatment, Diagnosis & More
https://pheopara.org/education/paraganglioma
Paragangliomas, if detected early, can be successfully treated and managed in the vast majority of cases. […] The prognosis for these patients is highly variable and can be based on the location of the tumors, genetic status, among other factors. […] There are currently no cures for cancerous paraganglioma. However, existing treatment options may reduce the tumors and prolong survival. […] All paraganglioma have the potential to become metastatic, or spread to other parts of the body. This happens in approximately 15-25% of cases. […] The prognosis is highly variable and is dependent upon the size of the primary tumor (tumors larger than 5-6 cm are more likely to metastasize), levels of methoxytyramine (a metabolite of the neurotransmitter dopamine which can be measured in the blood), and genetic status. […] Some patients live for decades with metastatic paraganglioma. […] Treatment of metastatic para can include surgery, MIBG therapy, PRRT therapy (Lutathera), chemotherapy, and others.
#14 Paraganglioma Symptoms, Treatment, Diagnosis & More
https://pheopara.org/education/paraganglioma
Paragangliomas, if detected early, can be successfully treated and managed in the vast majority of cases. […] The prognosis for these patients is highly variable and can be based on the location of the tumors, genetic status, among other factors. […] There are currently no cures for cancerous paraganglioma. However, existing treatment options may reduce the tumors and prolong survival. […] All paraganglioma have the potential to become metastatic, or spread to other parts of the body. This happens in approximately 15-25% of cases. […] The prognosis is highly variable and is dependent upon the size of the primary tumor (tumors larger than 5-6 cm are more likely to metastasize), levels of methoxytyramine (a metabolite of the neurotransmitter dopamine which can be measured in the blood), and genetic status. […] Some patients live for decades with metastatic paraganglioma. […] Treatment of metastatic para can include surgery, MIBG therapy, PRRT therapy (Lutathera), chemotherapy, and others.
#15
https://link.springer.com/article/10.1007/s12022-024-09830-3
Various histological features have been reported to be associated with an increased risk of PPGL metastasis, including invasion of soft tissue and blood vessels, particular architectural patterns including hypercellularity and large confluent nests, comedo-type necrosis, and a high mitotic count or Ki-67 proliferative index. […] Understanding the TME in PPGLs may also improve the application of targeted immunotherapies for metastatic diseases, though this area of research is still rudimentary and requires further exploration. […] International studies are essential to validate these biomarkers and develop a robust prediction model for metastatic disease.
#16 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
The rate of metastatic disease is extremely variable. […] However, in a recent retrospective study conducted on a large series of 169 metastatic PPGLs, the authors did not confirm SDHB mutation as a major prognostic parameter in metastatic disease, suggesting the potential role of other molecular events in tumor progression. […] The available literature concerning clinical features, secretory phenotype, and tumor morphological characteristics is controversial as well. […] Some histological features, such as tumor necrosis, mitoses over three per ten high-power fields (HPF), high cellularity, capsular invasion, and vascular or adipose tissue invasions have been proposed as predictive markers of more aggressive tumors. […] The proliferation marker, Ki67, has also been used to predict the metastatic behavior of PPGLs. […] The authors found a positive correlation between GAPP score and metastatic potential and a negative correlation with metastasis-free interval.
#17
https://link.springer.com/article/10.1007/s12022-024-09830-3
The malignant form of the disease remains challenging to predict and treat, as there are no established histopathological criteria to assess the risk of progression nor are there effective treatments available. […] Although these prediction systems have their advantages, they generally have limited positive predictive value for clinical behavior and outcomes in PPGL patients. […] The mechanisms of somatic genetic alterations leading to tumorigenesis or malignant transformation are not fully understood. […] Activation of the telomerase gene and ATRX loss of function variants have been associated with poor prognosis in PPGL. […] Recent studies reported that mechanisms of immortalization, frequently observed in carcinomas, involving telomere deregulation are implicated in the metastatic progression of PPGLs.
#18 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
The rate of metastatic disease is extremely variable. […] However, in a recent retrospective study conducted on a large series of 169 metastatic PPGLs, the authors did not confirm SDHB mutation as a major prognostic parameter in metastatic disease, suggesting the potential role of other molecular events in tumor progression. […] The available literature concerning clinical features, secretory phenotype, and tumor morphological characteristics is controversial as well. […] Some histological features, such as tumor necrosis, mitoses over three per ten high-power fields (HPF), high cellularity, capsular invasion, and vascular or adipose tissue invasions have been proposed as predictive markers of more aggressive tumors. […] The proliferation marker, Ki67, has also been used to predict the metastatic behavior of PPGLs. […] The authors found a positive correlation between GAPP score and metastatic potential and a negative correlation with metastasis-free interval.
#19 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
For patients with metastatic PPGL, the 5-year survival rate was lower than 50%. Metastasis can occur in months even decades after the initial diagnosis. Thus, a proportion of patients with PPGL was considered as non-metastatic before surgery, while they were identified to have metastasis during follow up. It is of great significance to predict the metastatic potential in early stage, not only evaluate the risk of metastasis as well as survival and prognosis, but also guide doctors in taking active surgical intervention and strict follow-up. […] A precise prediction of metastatic potential would be important. […] Prediction of PPGL metastatic potential remains a clinical challenge. Although many relevant indicators have been proved to be related to the metastasis of PPGL, none of them is 100% predictive; algorithms including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) grading system, the grading system for adrenal pheochromocytoma and paraganglioma (GAPP), the modified grading system for adrenal pheochromocytoma and paraganglioma (M-GAPP), the COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system and ASES scoring system had been proposed, but previous studies had demonstrated that reproducibility of these systems needs to be validated in multicenter studies.
#20 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. […] Actually, neither GAPP nor M-GAPP grading system had a credible prediction accuracy rate of metastatic tumors. Both of them were insufficient and need to be further validated in multicenter studies. It is of urgent need to establish new predictive models to evaluate metastatic potential for PPGL. […] The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features (tumor size, necrosis, vascular invasion) combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival.
#21
https://link.springer.com/article/10.1007/s12022-024-09830-3
The malignant form of the disease remains challenging to predict and treat, as there are no established histopathological criteria to assess the risk of progression nor are there effective treatments available. […] Although these prediction systems have their advantages, they generally have limited positive predictive value for clinical behavior and outcomes in PPGL patients. […] The mechanisms of somatic genetic alterations leading to tumorigenesis or malignant transformation are not fully understood. […] Activation of the telomerase gene and ATRX loss of function variants have been associated with poor prognosis in PPGL. […] Recent studies reported that mechanisms of immortalization, frequently observed in carcinomas, involving telomere deregulation are implicated in the metastatic progression of PPGLs.
#22 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. […] Actually, neither GAPP nor M-GAPP grading system had a credible prediction accuracy rate of metastatic tumors. Both of them were insufficient and need to be further validated in multicenter studies. It is of urgent need to establish new predictive models to evaluate metastatic potential for PPGL. […] The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features (tumor size, necrosis, vascular invasion) combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival.
#23 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Pheochromocytoma and paraganglioma (PPGL) represent a group of rare neuroendocrine tumors known for their potential to metastasize. […] Our primary objectives were to delineate the long-term clinical outcomes and pinpoint key prognostic determinants. […] A salient finding was that surgical interventions targeting metastatic lesions significantly improved prognosis. […] Further analysis revealed that a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) exceeding 7 closely associated with unfavorable outcomes. […] The value of the PASS score as an informative prognostic tool was evident, suggesting its utility in shaping future therapeutic approaches. […] The prognosis and survival rates for these patients are not well-established. […] Our analysis revealed two main findings.
#24 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. […] Actually, neither GAPP nor M-GAPP grading system had a credible prediction accuracy rate of metastatic tumors. Both of them were insufficient and need to be further validated in multicenter studies. It is of urgent need to establish new predictive models to evaluate metastatic potential for PPGL. […] The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features (tumor size, necrosis, vascular invasion) combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival.
#25 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
The rate of metastatic disease is extremely variable. […] However, in a recent retrospective study conducted on a large series of 169 metastatic PPGLs, the authors did not confirm SDHB mutation as a major prognostic parameter in metastatic disease, suggesting the potential role of other molecular events in tumor progression. […] The available literature concerning clinical features, secretory phenotype, and tumor morphological characteristics is controversial as well. […] Some histological features, such as tumor necrosis, mitoses over three per ten high-power fields (HPF), high cellularity, capsular invasion, and vascular or adipose tissue invasions have been proposed as predictive markers of more aggressive tumors. […] The proliferation marker, Ki67, has also been used to predict the metastatic behavior of PPGLs. […] The authors found a positive correlation between GAPP score and metastatic potential and a negative correlation with metastasis-free interval.
#26 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
The evaluation of metastatic potential is a research concern. Being the earliest grading system, the establishment of PASS system is of great significance and provides a foundation for subsequent research. Although metastatic prediction results of the PASS system are not satisfactory, the non-metastatic prediction ability makes it a great value in specific clinical applications. […] Actually, neither GAPP nor M-GAPP grading system had a credible prediction accuracy rate of metastatic tumors. Both of them were insufficient and need to be further validated in multicenter studies. It is of urgent need to establish new predictive models to evaluate metastatic potential for PPGL. […] The COPPs (COmposite Pheochromocytoma/paraganglioma Prognostic Score) scoring system, proposed by Pierre in 2019, is composed of three clinical-histopathological features (tumor size, necrosis, vascular invasion) combined with proliferation index PS100 and SDHB inactivation to predict PHEO/PGL metastasis risk and progression-free survival.
#27 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. […] Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#28 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma […] Background: Malignant pheochromocytoma and paraganglioma (PPGL) are rare tumors with few prognostic tools. This study aimed to construct nomograms for predicting 3- and 5-year survival for patients with malignant PPGL. […] Results: Age, gender, tumor type, tumor stage, or surgery were independent prognostic factors for OS in patients with malignant PPGL, while age, tumor stage, or surgery were independent prognostic factors for CSS (P <.05). Based on these factors, we successfully constructed the OS and CSS nomograms. The C-indexes were 0.747 and 0.742 for the OS and CSS nomograms, respectively. In addition, both the calibration curves and ROC curves for the model exhibited reliable performance.
#29 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
Conclusion: We successfully constructed nomograms for predicting the OS and CSS of patients with malignant PPGL. The nomograms could inform personalized clinical management of the patients. […] The prominent risk factors determined by the multivariate analysis were applied to construct nomograms that could predict the 3- and 5-year OS and CSS for PPGL. The nomogram used for OS prediction showed that prognosis was mainly affected by the tumor stage followed by age, tumor type, surgery and gender. Similarly, the nomogram for CSS indicated that tumor stage was also the most significant factor affecting prognosis, followed by age and surgery. […] Our study found that PPGL was highly diverse in the clinical course. Compared with the PHEO or PGL, Extra-PGL showed better OS, but moderate CSS.
#30 Frontiers | Prognostic Nomograms for Predicting Overall Survival and CancerâSpecific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.684668/full
In conclusion, we have successfully established nomograms for the prediction of 3- and 5-year OS and CSS in patients with PPGL. The nomogram proved to be accurate and reliable in the prediction of the disease outcome. The nomogram can be used as an independent tool to assess the prognosis and guide personalized follow-up for clinical management of malignant PPGL patients.
#31 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
Pheochromocytoma and paraganglioma (PPGL) represent a group of rare neuroendocrine tumors known for their potential to metastasize. […] Our primary objectives were to delineate the long-term clinical outcomes and pinpoint key prognostic determinants. […] A salient finding was that surgical interventions targeting metastatic lesions significantly improved prognosis. […] Further analysis revealed that a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) exceeding 7 closely associated with unfavorable outcomes. […] The value of the PASS score as an informative prognostic tool was evident, suggesting its utility in shaping future therapeutic approaches. […] The prognosis and survival rates for these patients are not well-established. […] Our analysis revealed two main findings.
#32 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
The 5-, 10-, and 15-year survival rates after metastasis or recurrent diagnosis were 73.3%, 62.9%, and 31.4%, respectively, which is consistent with previous studies. […] Patients who underwent surgery for metastasis or recurrent lesion had a significantly better prognosis. […] Our study adds to this literature by demonstrating that surgery intervention is associated with better outcomes in patients with metastatic or recurrent PPGL. […] In addition, patients with PASS7 for the primary tumor had a significantly worse prognosis. […] Our findings suggest that surgical intervention is a pivotal factor associated with improved prognosis and higher survival rates.
#33 Long-term outcomes and prognostic factors of metastatic or recurrent pheochromocytoma and paraganglioma: a 20-year review in a single institution | Scientific Reports
https://www.nature.com/articles/s41598-024-75354-9
The 5-, 10-, and 15-year survival rates after metastasis or recurrent diagnosis were 73.3%, 62.9%, and 31.4%, respectively, which is consistent with previous studies. […] Patients who underwent surgery for metastasis or recurrent lesion had a significantly better prognosis. […] Our study adds to this literature by demonstrating that surgery intervention is associated with better outcomes in patients with metastatic or recurrent PPGL. […] In addition, patients with PASS7 for the primary tumor had a significantly worse prognosis. […] Our findings suggest that surgical intervention is a pivotal factor associated with improved prognosis and higher survival rates.
#34 Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE
https://www.mdpi.com/2072-6694/11/7/909
Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE […] Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. […] The median overall survival (OS) was 49.6 (range 8.2â139) months and median progression-free survival (PFS) was 21.6 (range 6.7â138) months. […] Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). [...] High Ki-67 (â¥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.
#35 177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma in: Endocrine Connections Volume 9 Issue 9 (2020)
https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0292.xml
177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. […] Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax 21, baseline SUVmax 21 can be used to predict early response to PRRT. […] The median duration of follow up was 27 months (range: 1162) from the start of PRRT. The overall survival was 100% whereas median PFS was not reached. […] Median PFS was 14 months in PCC whereas median PFS was not achieved in HNPGL. […] The baseline mean SUVmax significantly predicted response (CD) to PRRT with the area under the curve (AUC) of 0.939. […] Baseline mean SUVmax of 21 on 68Ga-DOTATATE significantly predicted response to subsequent PRRT in our study. […] Patients with baseline mean SUVmax of 21 also tended to have longer PFS.
#36 Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE
https://www.mdpi.com/2072-6694/11/7/909
Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE […] Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. […] The median overall survival (OS) was 49.6 (range 8.2â139) months and median progression-free survival (PFS) was 21.6 (range 6.7â138) months. […] Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). [...] High Ki-67 (â¥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.
#37 177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma in: Endocrine Connections Volume 9 Issue 9 (2020)
https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0292.xml
177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. […] Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax 21, baseline SUVmax 21 can be used to predict early response to PRRT. […] The median duration of follow up was 27 months (range: 1162) from the start of PRRT. The overall survival was 100% whereas median PFS was not reached. […] Median PFS was 14 months in PCC whereas median PFS was not achieved in HNPGL. […] The baseline mean SUVmax significantly predicted response (CD) to PRRT with the area under the curve (AUC) of 0.939. […] Baseline mean SUVmax of 21 on 68Ga-DOTATATE significantly predicted response to subsequent PRRT in our study. […] Patients with baseline mean SUVmax of 21 also tended to have longer PFS.
#38 177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma in: Endocrine Connections Volume 9 Issue 9 (2020)
https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0292.xml
177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. […] Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax 21, baseline SUVmax 21 can be used to predict early response to PRRT. […] The median duration of follow up was 27 months (range: 1162) from the start of PRRT. The overall survival was 100% whereas median PFS was not reached. […] Median PFS was 14 months in PCC whereas median PFS was not achieved in HNPGL. […] The baseline mean SUVmax significantly predicted response (CD) to PRRT with the area under the curve (AUC) of 0.939. […] Baseline mean SUVmax of 21 on 68Ga-DOTATATE significantly predicted response to subsequent PRRT in our study. […] Patients with baseline mean SUVmax of 21 also tended to have longer PFS.
#39 177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma in: Endocrine Connections Volume 9 Issue 9 (2020)
https://ec.bioscientifica.com/view/journals/ec/9/9/EC-20-0292.xml
The defined daily dose (DDD) of anti-hypertensives decreased in six of nine (66%) patients while increased in the remaining three (PD). […] In patients with associated PNET, the mean SUVmax of PNET decreased on follow up imaging, despite progressive PPGL disease in one patient. […] The most common adverse effects observed were nausea-vomiting and weight loss. […] None of the patients had transient or permanent nephrotoxicity.
#40 Paraganglioma Symptoms, Treatment, Diagnosis & More
https://pheopara.org/education/paraganglioma
Paragangliomas, if detected early, can be successfully treated and managed in the vast majority of cases. […] The prognosis for these patients is highly variable and can be based on the location of the tumors, genetic status, among other factors. […] There are currently no cures for cancerous paraganglioma. However, existing treatment options may reduce the tumors and prolong survival. […] All paraganglioma have the potential to become metastatic, or spread to other parts of the body. This happens in approximately 15-25% of cases. […] The prognosis is highly variable and is dependent upon the size of the primary tumor (tumors larger than 5-6 cm are more likely to metastasize), levels of methoxytyramine (a metabolite of the neurotransmitter dopamine which can be measured in the blood), and genetic status. […] Some patients live for decades with metastatic paraganglioma. […] Treatment of metastatic para can include surgery, MIBG therapy, PRRT therapy (Lutathera), chemotherapy, and others.
#41 Paraganglioma Symptoms, Treatment, Diagnosis & More
https://pheopara.org/education/paraganglioma
Paragangliomas, if detected early, can be successfully treated and managed in the vast majority of cases. […] The prognosis for these patients is highly variable and can be based on the location of the tumors, genetic status, among other factors. […] There are currently no cures for cancerous paraganglioma. However, existing treatment options may reduce the tumors and prolong survival. […] All paraganglioma have the potential to become metastatic, or spread to other parts of the body. This happens in approximately 15-25% of cases. […] The prognosis is highly variable and is dependent upon the size of the primary tumor (tumors larger than 5-6 cm are more likely to metastasize), levels of methoxytyramine (a metabolite of the neurotransmitter dopamine which can be measured in the blood), and genetic status. […] Some patients live for decades with metastatic paraganglioma. […] Treatment of metastatic para can include surgery, MIBG therapy, PRRT therapy (Lutathera), chemotherapy, and others.
#42 Paraganglioma Symptoms, Treatment, Diagnosis & More
https://pheopara.org/education/paraganglioma
Paragangliomas, if detected early, can be successfully treated and managed in the vast majority of cases. […] The prognosis for these patients is highly variable and can be based on the location of the tumors, genetic status, among other factors. […] There are currently no cures for cancerous paraganglioma. However, existing treatment options may reduce the tumors and prolong survival. […] All paraganglioma have the potential to become metastatic, or spread to other parts of the body. This happens in approximately 15-25% of cases. […] The prognosis is highly variable and is dependent upon the size of the primary tumor (tumors larger than 5-6 cm are more likely to metastasize), levels of methoxytyramine (a metabolite of the neurotransmitter dopamine which can be measured in the blood), and genetic status. […] Some patients live for decades with metastatic paraganglioma. […] Treatment of metastatic para can include surgery, MIBG therapy, PRRT therapy (Lutathera), chemotherapy, and others.
#43 The systems of metastatic potential prediction in pheochromocytoma and paraganglioma
https://pmc.ncbi.nlm.nih.gov/articles/PMC7136918/
Ultimately, the ASES system showed a low sensibility of 61% and a specificity of 80%. The prediction accuracy rate of non-metastatic PPGL and metastatic PPGL was 97% and 18%, respectively. […] Many indicators, such as histopathology, genetic mutations, biomarkers, and clinical characteristics, have been declared to be associated with metastasis, but none of the individual factors was 100% correlated. So, it is a challenge to establish a new, convenient, highly specific and standard evaluation system by combining multiple influencing factors.
#44
https://link.springer.com/article/10.1007/s12022-024-09830-3
Various histological features have been reported to be associated with an increased risk of PPGL metastasis, including invasion of soft tissue and blood vessels, particular architectural patterns including hypercellularity and large confluent nests, comedo-type necrosis, and a high mitotic count or Ki-67 proliferative index. […] Understanding the TME in PPGLs may also improve the application of targeted immunotherapies for metastatic diseases, though this area of research is still rudimentary and requires further exploration. […] International studies are essential to validate these biomarkers and develop a robust prediction model for metastatic disease.
#45
https://link.springer.com/article/10.1007/s12022-024-09830-3
Various histological features have been reported to be associated with an increased risk of PPGL metastasis, including invasion of soft tissue and blood vessels, particular architectural patterns including hypercellularity and large confluent nests, comedo-type necrosis, and a high mitotic count or Ki-67 proliferative index. […] Understanding the TME in PPGLs may also improve the application of targeted immunotherapies for metastatic diseases, though this area of research is still rudimentary and requires further exploration. […] International studies are essential to validate these biomarkers and develop a robust prediction model for metastatic disease.
#46 Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma
https://www.mdpi.com/2227-9059/10/8/1813
Pheochromocytomas and paragangliomas are endocrine tumors belonging to the family of neural crest cell-derived neoplasms. They have an extremely variable clinical course, characterized by a non-negligible percentage of relapse and/or metastasis after radical surgery. To date, there are no reliable methods to predict the metastatic potential of these neoplasms, despite several clinical, molecular, and histopathological factors that have been extensively studied in the literature as predictors of the recurrence and/or metastasis in these neoplasms with different performances and results. […] In conclusion, we underlined the importance of simple and validated tools to better define disease aggressiveness and establish tailored patientsâ treatments and follow-ups. […] PPGLs are also very heterogeneous in the clinical course with a variable prognosis concerning the development of metastases. Despite most of these neoplasms are radically cured by surgery, all PPGLs have potentially metastatic properties, and no reliable clinical, histopathological, or biochemical predictors are established to determine with certainty whether a PPGL could be potentially metastatic. […] Although many studies have examined the potential prognostic role of various clinical, biochemical, genetic, and histopathological features, there is not a single feature that can be used alone to reliably predict tumor recurrence and, therefore, guide clinical practice.