scholarly journals Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 508 ◽  
Author(s):  
Sara Bedrose ◽  
Marilyne Daher ◽  
Lina Altameemi ◽  
Mouhammed Amir Habra
Keyword(s):  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Genetic Alterations ◽  
Disease Stage ◽  
Proliferation Index ◽  
Resection Margins ◽  
Ki 67 ◽  
Platinum Based Chemotherapy

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation index). Mitotane has been the mainstay adjuvant therapy of ACC. However, the use of mitotane is based on retrospective and occasionally conflicting evidence. As mitotane levels can take a few months before reaching therapeutic levels, there is an emerging practice of combining platinum-based chemotherapy with mitotane in the adjuvant setting. Retrospective data indicate that radiotherapy is an option for select patients, particularly those with positive resection margins. There are multiple knowledge gaps in selecting patients for adjuvant therapy. It is of great importance to establish risk calculators to predict recurrence and to implement molecular profiling of ACC to guide adjuvant therapy. The role of immunotherapy in metastatic ACC is emerging and if deemed efficacious, then future studies will be needed to ascertain the role of adjuvant immunotherapy in ACC.

scholarly journals PCSK9 Inhibitors for the Management of Mitotane-Induced Hypercholesterolemia in Adrenocortical Carcinoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A310-A311
Author(s):  
John A Aurora ◽  
Feyza Erenler ◽  
Stephany Matta ◽  
Ronald M Lechan
Keyword(s):  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Mitotic Rate ◽  
Adrenocortical Cancer ◽  
Pcsk9 Inhibitors ◽  
Ki 67 ◽  
Pcsk9 Inhibitor ◽  
Cyp3a4 Inducer ◽  
Coa Reductase

Abstract Background: After surgical resection in adrenocortical carcinoma (ACC), mitotane is often used as adjuvant therapy. However, mitotane can cause adverse effects, such as inducing hypercholesterolemia by stimulating HMG-CoA reductase. In addition, mitotane is a strong CYP3A4 inducer which presents a challenge with statins, such as lovastatin, simvastatin, and atorvastatin. We present a case using a PCSK9 inhibitor in mitotane-induced hypercholesterolemia which was refractory to the maximum dose of rosuvastatin. Clinical Case: A laparoscopic left adrenalectomy was performed on a 45-year old female with Stage 3 (T3, NX, M0) ACC (4.5 x 3.4 x 3.2 cm). Her ACC was determined to be high grade with a mitotic rate 20/50 HPF and Ki-67 of 18.7% with lymphovascular invasion and tumor invasion of periadrenal adipose tissue. Following surgical resection, she started adjuvant therapy mitotane and oral hydrocortisone replacement, as well as 6 weeks of radiation therapy. Prior to starting mitotane, her LDL-C was 133 mg/dL (normal range <130 mg/dL) and treated with simvastatin 40 mg daily. A drug interaction was identified between simvastatin and mitotane, with mitotane reducing effects of simvastatin via CYP3A4 induction, so rosuvastatin 10 mg daily was started instead. A trial of combination rosuvastatin and ezetimibe was used; however, patient discontinued ezetimibe due to reported side effects. As the dose of mitotane increased to achieve a blood concentration of 14–20 mcg/mL, LDL-C simultaneously increased along with a corresponding dose increase of rosuvastatin. While being on mitotane 2 g daily and rosuvastatin 40 mg daily, her lipids peaked with LDL-C 219 mg/dL. The decision was made to start evolocumab administered as 140 mg subcutaneously every 2 weeks in addition to rosuvastatin 40 mg daily. After 4 months of therapy with combination evolocumab and rosuvastatin, her LDL-C decreased to 111 mg/dL, a 49% reduction, while achieving a mitotane concentration of 13 mcg/mL using 4 g daily. Conclusion: Utilizing a PCSK9 inhibitor, such as evolocumab, allows the dose of mitotane to be increased to achieve a therapeutic level while maintaining adequate control of cholesterol. With options for management of mitotane-induced hypercholesterolemia being limited, off-label use of a PCSK9 inhibitor can be justified clinically as moderate LDL-C reduction has also been shown in a prior published case report (1). Evolocumab is a well-tolerated subcutaneous injection, and should be considered for patients with resistant hypercholesterolemia while on mitotane. References: (1) Tsakiridou ED, Liberopoulos E, Giotaki Z, et al. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor use in the management of resistant hypercholesterolemia induced by mitotane treatment for adrenocortical cancer. J Clin Lipidol. 2018;12(3):826–829.

scholarly journals Predictors of Survival in Adrenocortical Carcinoma: An Analysis From the National Cancer Database

2018 ◽  
Vol 103 (9) ◽  
pp. 3566-3573 ◽  
Author(s):  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Subhashini Yaturu ◽  
Electron Kebebew
Keyword(s):  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Poor Prognosis ◽  
Stage Iv ◽  
Tumor Grade ◽  
Disease Stage ◽  
Survival Outcomes ◽  
National Cancer Database ◽  
Stage Iv Disease ◽  
Comorbidity Index

Abstract Context Adrenocortical carcinoma (ACC) is rare; knowledge about prognostic factors and survival outcomes is limited. Objective To describe predictors of survival and overall survival (OS) outcomes. Design and Patients Retrospective analysis of data from the National Cancer Database (NCDB) from 2004 to 2015 on 3185 patients with pathologically confirmed ACC. Main Outcome Measures Baseline description, survival outcomes, and predictors of survival were evaluated in patients with ACC. Results Median age at ACC diagnosis was 55 (range: 18 to 90) years; did not differ significantly by sex or stage of the disease at diagnosis. On multivariate analysis, increasing age, higher Charlson-Deyo comorbidity index score, high tumor grade, and no surgical therapy (all P < 0.0001); and stage IV disease (P = 0.002) and lymphadenectomy during surgery (P = 0.02) were associated with poor prognosis. Patients with stage I-III disease treated with surgical resection had significantly better median OS (63 vs 8 months; P < 0.001). In stage IV disease, better median OS occurred in patients treated with surgery (19 vs 6 months; P < 0.001), and postsurgical radiation (29 vs 10 months; P < 0.001) or chemotherapy (22 vs 13 months; P = 0.004). Conclusion OS varied with increasing age, higher comorbidity index, grade, and stage of ACC at presentation. There was improved survival with surgical resection of primary tumor, irrespective of disease stage; postsurgical chemotherapy or radiation was of benefit only in stage IV disease.

A Clinicopathologic Study on the Role of Estrogen, Progesterone, and Their Classical and Nonclassical Receptors in Cutaneous Neurofibromas of Individuals With Neurofibromatosis 1

2020 ◽  
Author(s):  
Rafaela E Rozza-de-Menezes ◽  
Lilian M Almeida ◽  
Raquel M Andrade-Losso ◽  
Gustavo de Souza Vieira ◽  
Orlando H K Siqueira ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Laboratory Data ◽  
Serum Levels ◽  
Neurofibromatosis 1 ◽  
Proliferation Index ◽  
Computer Assisted ◽  
Ki 67 ◽  
Clinicopathologic Study ◽  
Cutaneous Neurofibromas

Abstract Objectives To evaluate the expression of progesterone receptor (PR), estrogen receptor (ER), and G protein–coupled estrogen receptor 1 (GPER-1) in cutaneous neurofibromas (cNFs) and their correlation with demographic, clinical, and laboratory data of individuals with neurofibromatosis 1 (NF1). The association of PROGINS polymorphism and PR expression in cNFs, as well as the serum steroidal hormones and the number of cNFs, was investigated. Methods The sample comprised 80 large and 80 small cNFs from 80 individuals with NF1. PR, ER, GPER-1, and Ki-67 expression were investigated by immunohistochemistry in tissue micro- and macroarrays and quantified using a digital computer-assisted method. The number of cNFs, the levels of serum 17β estradiol and progesterone, and the PROGINS polymorphism were identified. Results Twelve (8.5%) small cNFs were weakly positive for ER, 131 (92.3%) cNFs expressed PR, and all (100%) cNFs expressed GPER-1. Large cNFs showed a higher expression of PR (P < .0001) and GPER-1 (P = .019) and had a higher intensity of staining for these receptors (P < .0001). The cell proliferation index was positively correlated with PR (P = .001). Persons with more cNFs had higher serum levels of progesterone (P = .001). Conclusions These findings emphasize the role of estrogen and progesterone in cNF development and suggest that these hormones may act on cNF cells via a noncanonical pathway through GPER-1.

scholarly journals Ghost cell odontogenic carcinoma: Role of p53 as predictor of progression

2020 ◽  
Vol 10 (1) ◽  
pp. 1675-1678
Author(s):  
Pallavi Srivastava ◽  
Nidhi Anand ◽  
Nuzhat Husain
Keyword(s):  
Distant Metastases ◽  
Proliferation Index ◽  
Ghost Cell ◽  
Ki 67 ◽  
Local Recurrences ◽  
Odontogenic Carcinoma ◽  
Fibular Flap ◽  
Slow Growing

Ghost cell odontogenic carcinoma (GCOC) a rare malignant Odontogenic Carcinoma with an unpredictable behaviour presenting with local recurrences and distant metastases, to best of our knowledge about 38 cases have been reported in the past. This is an additional case of GCOC in a 25-year old female presented with a slow-growing mandibular swelling since 9 months with restricted jaw mobility. The CT scan showed an ill-defined osteodestructive lesion in the mandible. The histological examination confirms the diagnoses as a GCOC. Immunohistochemical examination was performed for Ki-67 proliferation index and p53 a predictor of progression. This case was managed by wide surgical resection of tumor and reconstruction of the defect by free fibular flap. Six months follow- up period shows no signs of recurrence. GCOC is rare Odontogenic Carcinoma with unpredictable behaviour however p53 & Ki67 proliferation index can predict the progression of tumor and help in differentiation from benign precursor lesions as early diagnosis & treatment of GCOC is necessary to prevent local recurrences & distant metastases.

Impact of timing of adjuvant chemotherapy initiation on survival in pancreatic adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Sofia Palacio ◽  
Caroline Ripat ◽  
Heather Stuart ◽  
Danny Yakoub ◽  
Nipun B. Merchant
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Surgical Resection ◽  
Hazard Model ◽  
Disease Stage ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard

355 Background: Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer death. Surgical resection followed by adjuvant chemotherapy has been the standard of care. Due to the significant risk of morbidity following pancreatic surgery, initiation of adjuvant chemotherapy is often delayed. Prior prospective adjuvant trials have suggested that adjuvant therapy can be initiated as late as 12 weeks without detriment, but data regarding the effectiveness of beginning adjuvant therapy beyond that time remains unknown. Methods: We retrospectivelyreviewed data from the National Cancer Data Base (2004-2014) and included adult patients (pts) with PDAC with pathologic stage I-IIB who underwent surgical resection with curative intent. The primary outcome was overall survival (OS) based on time to adjuvant chemotherapy post-surgery as defined by postoperative weeks. Data were analyzed using Cox proportional hazard model and Kaplan-Meier survival curves. Results: 5279 pts. had surgery alone and 4,537 pts. received adjuvant chemotherapy. The median age was 64 years. 52% were male, 88% were white, 46% were treated at comprehensive community cancer centers. The primary surgical approach was whipple procedure in 61% of pts. 63% pts. received single agent chemotherapy and the mean time from surgery to chemotherapy was 61 days. Adjuvant chemotherapy was associated with improved OS irrespective of disease stage compared to those undergoing surgery alone (median OS for surgery alone 14 months vs adjuvant chemotherapy 21 months, p < 0.001). Cox proportional hazard model controlling for stage, surgical technique, lymph node dissection and margin status revealed improved OS in pts. receiving adjuvant chemotherapy. No significant differences in OS were seen for pts. starting adjuvant chemotherapy at 3, 6, 9, 12, 16, 20 or 24 weeks after surgical resection. Conclusions: Current guidelines recommend initiation of adjuvant chemotherapy prior to 12 weeks after pancreatic resection. Initiating adjuvant chemotherapy even up to six months post-operatively improves OS compared to those undergoing surgery alone. Our data supports the use of adjuvant chemotherapy if indicated regardless of time of surgery.

scholarly journals Oncocytic Variant of Adrenocortical Carcinoma: Case Report of a Rare Malignancy

2020 ◽  
pp. 1-4
Author(s):  
Sarath Sistla ◽  
Balamourougan Krishnaraj ◽  
Gomathi Shankar ◽  
Jigish Ruparelia ◽  
Prakriti Giri ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Histopathological Examination ◽  
Large Mass ◽  
Disease Stage ◽  
Surgical Specimen ◽  
Oncocytic Variant ◽  
Rare Malignancy ◽  
Oncocytic Neoplasm

Adrenocortical carcinoma is a rare cancer. Oncocytic tumors of the adrenal gland are rarer. Most Oncocytic Adrenal Neoplasms are benign and carry favourable prognosis. They are classified as oncocytoma, oncocytic neoplasm of uncertain malignant potential and oncocytic adrenal carcinoma. The malignant nature of oncocytic neoplasm of adrenal gland can only be confirmed on histopathology. We report a case of a 55-year-old male with newly diagnosed hypertension being evaluated for left adrenal mass concerning for adrenocortical carcinoma. Open radical left adrenalectomy and nephrectomy was done and histopathology confirmed oncocytic variant of adrenocortical carcinoma based on Lin-Weiss-Bisceglia scoring system which has been developed particularly for oncocytic type of tumor. Though rare, oncocytic neoplasm has to be considered as one of the differential diagnoses of adrenocortical mass, especially those presenting as a large mass because malignant oncocytic neoplasm of adrenal gland as large as 23cm have been reported. Imaging modalities like ultrasonography, computed tomography or magnetic resonance imaging, though useful in evaluating an adrenocortical mass, cannot predict malignant nature of an oncocytic neoplasm. Diagnosis of adrenocortical carcinoma is therefore reliably made only after histopathological examination of the surgical specimen. Surgical resection in those presenting with nonmetastatic resectable disease remains the mainstay of ACC treatment. Oncocytic ACC compared with conventional ACCs matched for age, gender, disease stage and status of surgical resection, shows significant better overall survival thus representing more indolent variant of an aggressive and often fatal disease.

scholarly journals PREDICTIVE RELAPSE MODEL IN PATIENTS WITH LUMINAL HER2-NEGATIVE BREAST CANCER

2020 ◽  
pp. 61-73
Author(s):  
M.Kh. Torosyan ◽  
T.V. Shevchenko ◽  
V.V. Rodionov ◽  
Yu.G. Savinov ◽  
Yu.A. Veryaskina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Model ◽  
Prognostic Index ◽  
Cancer Recurrence ◽  
Disease Stage ◽  
Luminal Breast Cancer ◽  
Her2 Overexpression ◽  
Ki 67 ◽  
Expression Levels

Luminal HER2-negative breast cancer (BC) detected at early stages is characterized by a relatively favorable course. However, in some cases, there may be a relapse of the disease regardless of the treatment. The aim of the study was to identify predictors of recurrence of primary resectable luminal HER2-negative breast cancer. Materials and Methods. The authors examined biopsies of patients’ breast tumors (n=158) with luminal HER2-negative breast cancer, stage T1-2N0-1M0, as well as anamnestic data of patients. All women were divided into 2 groups: with disease recurrence within the next 5 years after surgery (n=53) and relapse-free patients (n=105). Macroscopic tumor characteristics, its malignancy, total malignancy score, Nottingham prognostic index, Ki-67, expression of receptors for estrogen and progesterone and their influence on relapse were studied. The authors analyzed expression levels of miRNA (miRNA-21, miRNA-221, miRNA-222, miRNA-155, miRNA-205, miRNA-20a, miRNA-125b, miRNA-146b, miRNA-200a) in tumor tissues. Statistical data processing was performed using Statistica 7 (StatSoft Inc., USA) and MedCalc (version 15.2) software. Results. Comparative analysis of miRNA expression levels between groups of patients with recurrent breast cancer (n=21) and relapse-free patients (n=20) revealed a statistically significant increase in the expression levels of miRNA-21, miRNA-205, miRNA-146b, and miRNA-200a in the group with recurrent disease. The authors established the predictive role of the ratios of the expression levels of potentially oncogenic and tumor suppressive miRNA-21/miRNA-155 and miRNA-21/miRNA-205, as well as the role of miRNA-20a in breast cancer recurrence in combination with Ki-67, disease stage, and primary tumor size. Based on the data obtained, they developed a prognostic model to determine the recurrence of primary operable luminal HER2-negative breast cancer. Conclusion. The created prognostic model allows to clearly stratify the prognosis of primary operable luminal HER2-negative breast cancer. Keywords: primary resectable luminal breast cancer without HER2 overexpression, recurrence prognosis, miRNA. Люминальный HER2-негативный рак молочной железы (РМЖ), выявленный на ранних стадиях, характеризуется относительно благоприятным течением. Однако в ряде случаев возникает рецидив заболевания независимо от проведенного лечения. Цель исследования – выявить предикторы рецидивирования первично операбельного люминального HER2-негативного РМЖ. Материалы и методы. Исследовались биоптаты опухолей молочной железы пациенток (n=158) с люминальным HER2-негативным РМЖ стадии T1-2N0-1M0, а также анамнестические данные пациенток. Все женщины были разделены на 2 группы: с рецидивом заболевания в течение последующих 5 лет после проведения операции (n=53) и с безрецидивным течением (n=105). Изучены макроскопические характеристики опухоли, степень злокачественности, суммарный балл злокачественности, Ноттингемский прогностический индекс, Ki-67, экспрессия рецепторов к эстрогену и прогестерону и их влияние на возникновение рецидива. Проведен анализ уровней экспрессии миРНК (миРНК-21, миРНК-221, миРНК-222, миРНК-155, миРНК-205, миРНК-20а, миРНК-125b, миРНК-146b, миРНК-200a) в тканях опухолей. Статистическая обработка данных произведена с помощью программ Statistica 7 (StatSoft Inc., США) и MedCalc (версия 15.2). Результаты. Сравнительный анализ уровней экспрессии миРНК между группами пациенток с рецидивом РМЖ (n=21) и безрецидивным течением (n=20) выявил статистически значимое повышение уровней экспрессии миРНК-21, миРНК-205, миРНК-146b и миРНК-200a в группе с рецидивом заболевания. Установлена предсказывающая роль соотношений уровней экспрессии потенциально онкогенных и онкосупрессорных миРНК-21/миРНК-155 и миРНК-21/миРНК-205, а также роль миРНК-20a в возникновении рецидива РМЖ в сочетании с Кi-67, стадией заболевания, размером первичной опухоли. На основе полученных данных разработана прогностическая модель определения рецидива первично операбельного люминального HER2-негативного РМЖ. Выводы. Созданная прогностическая модель позволяет четко стратифицировать прогноз первично операбельного люминального HER2-негативного РМЖ. Ключевые слова: первично операбельный люминальный рак молочной железы без гиперэкспрессии HER2, прогноз рецидива, миРНК.

scholarly journals Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma

2021 ◽  
Vol 43 (3) ◽  
pp. 2266-2275
Author(s):  
Vladislav Pavlov ◽  
Anastasiya Snezhkina ◽  
Dmitry Kalinin ◽  
Alexander Golovyuk ◽  
Anastasiya Kobelyatskaya ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Neck Region ◽  
Genetic Alterations ◽  
The Body ◽  
Proliferation Index ◽  
Recurrent Tumor ◽  
Sdhb Mutation ◽  
Ki 67 ◽  
Whole Exome ◽  
Tert Gene

Paragangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the potential to metastasize. To date, molecular mechanisms of paraganglioma progression remain elusive. We report a case of a 38-year-old woman with metastatic CPGL manifesting as a recurrent tumor with lymph node metastasis. The tumor was fast-growing and had a high Ki-67 proliferation index. Immunohistochemical (IHC) examination and whole-exome sequencing were performed for both recurrent tumor and metastasis. A germline pathogenic splice acceptor variant in the SDHB gene was found in the patient. Immunoreactivity of the SDHB subunit was weak diffuse in both samples, indicating deficiency of the succinate dehydrogenase. Moreover, the recurrent tumor exhibited loss of heterozygosity (LOH) at the SDHB locus, that is according to Knudson’s "two-hit" hypothesis of cancer causation. We also identified a rare somatic promotor mutation in the TERT gene associated with the tumor progression. Obtained results confirmed the indicative role of the germline SDHB mutation for metastatic CPGLs, as well as the potential prognostic value of the TERT promoter mutation.

The role of Ki-67 proliferation index vis-à-vis Oncotype DX.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e11055-e11055
Author(s):  
S. Sahebjam ◽  
R. Aloyz ◽  
D. Pilavdzic ◽  
M. Brisson ◽  
C. Ferrario ◽  
...  
Keyword(s):  
Oncotype Dx ◽  
Proliferation Index ◽  
Ki 67

Role of adjuvant therapy in resected gallbladder cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 452-452
Author(s):  
Mohamed Abdelrahim Muddathir Hassan ◽  
Nicha Wongjarupong ◽  
Cristobal T. Sanhueza ◽  
Mindy L. Hartgers ◽  
Fatima Hassan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Therapy ◽  
Gallbladder Cancer ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

452 Background: Surgical resection is the only curative treatment for patients with gallbladder cancer, despite surgical advances many patients ultimately develop recurrent disease. Management of resected gallbladder cancer mostly relies on single-arm trials and retrospective observations. The purpose of our study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer patients who have undergone surgical resection. Methods: Clinical data were collected on 251 patients who underwent surgical resection for stage I-III gallbladder cancer and presented to Mayo clinic from January 2000-December 2015. Patients were then classified into adjuvant treatment group and surveillance only group. Overall survival and recurrence were compared between the two groups. Results: 78 (31.1%) patients received adjuvant therapy while 173 patients were observed only. Patients who received adjuvant tended to be younger (63.0[SD 11] vs 66.2 [SD 13.1]), have higher stage, and underwent extended surgery. Most patients received chemoradiotherapy (55) with 5-Fluorouracil (67.3%) and capecitabine (25.5%) as radiosensitizing agents. 21 patients received additional adjuvant chemotherapy. 27% of patients received chemotherapy as the sole adjuvant treatment. The most common chemo regimens included gemcitabine (52.3%) and gemcitabine plus cisplatin combination (23.8%). On multivariate analysis patients > 65 years(HR 1.53 [1.07-2.19], p = 0.02), males (HR 1.7 [1.2-2.4], p = 0.003), positive margins (2.77 [1.69-4.38], p < 0.01), and stage III (HR 1.91 [1.35-2.70], p < 0.01) had worse overall survival. Patients who underwent extended radical resection (HR 0.73 [0.51-1.05], p = 0.09) had better overall survival. Adjuvant therapy had no statistical significant effect on overall survival (HR 1.10 [0.75-1.59], p = 0.63 or disease free survival (HR 1.05 [0.69-1.59], p = 0.81) on overall population. However, in stage IIIB, patients receiving adjuvant therapy had better overall survival (HR 0.51 [0.25-1.01], p = 0.05) and disease free survival (HR 0.45 [0.19-1.09], p = 0.06). Conclusions: In our study, adjuvant treatment, especially chemoradiation therapy, was only beneficial in patients with stage IIIb gallbladder cancer patients.

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