A Walk with Lu-177 PSMA: How Close we Have Reached from Bench to Bedside?

Metastatic castration-resistant prostate cancer (mCRPC) is a natural sequela in advanced prostate cancer following resistance to standard treatment regimes, where patients develop with rising PSA, bone pains, and high disease volume. Further palliative treatment is the need of the hour for ensuring disease control and quality of life. In recent times, many novel methods have been evolved for these patients. Endo-radioligand therapy with Lutetium 177 prostate-specific membrane antigen 617 (Lu-177 PSMA) based on the Theranostic concept has emerged as a promising tool among these. We present here the current status of Lu177-PSMA for mCRPC patient and future directions.

Nab-paclitaxel: An effective third-line chemotherapy in patients with advanced, unresectable gallbladder cancer.

BACKGROUND & OBJECTIVES: Gallbladder (GBC) is an aggressive form of cancer and most patients present with advanced unresectable disease due to lack of early signs and symptoms. This retrospective study was conducted to present the treatment outcomes with three lines of chemotherapies in a subset of patients with advanced, unresectable GBC with the primary objective to determine the response rates with nab-paclitaxel as the third-line chemotherapy after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 (oxaliplatin, leucovorin and 5-FU) therapy. Another objective was to evaluate the toxicity, progression-free survival (PFS) and overall survival (OS). METHODS: Treatment-naive patients with histologically proven inoperable GBC treated with gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel as the first-, second- and third-line chemotherapy were included in this study. The dose of gemcitabine and cisplatin or carboplatin was 1 g/m[2] on days 1 and 8 and 75 mg/m[2] (or target AUC of 5) on day 1, in a 21-day cycle. FOLFOX-4 was administered every two weeks and nab-paclitaxel was administered as 125 mg/m[2] on days 1, 8 and 15 in a 28-day cycle. RESULTS: There were eight men and 13 women with a median age of 57 yr who received nab-paclitaxel therapy. The overall response rate of the first-, second- and third-line chemotherapy was 61.9, 57.1 and 52.4 per cent, respectively. The median PFS for the gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy was 5.5, 5.4 and 2.9 months, respectively. The median OS with three lines of therapies was 14.0 months. Common Terminology Criteria (CTC) grade 3 or 4 haematological toxicities were observed in 28.6, 38.1 and 23.8 per cent of patients on gemcitabine/platinum, FOLFOX-4 and nab-paclitaxel therapy, respectively. INTERPRETATION & CONCLUSIONS: Our study suggests the clinical benefit of nab-paclitaxel chemotherapy in prolonging OS in a selected subgroup of advanced, unresectable GBC patients after failure of the first-line gemcitabine and platinum and the second-line FOLFOX-4 therapy.

Shared Decision-Making and Medicolegal Aspects: Delivering High-Quality Cancer Care in India.

It is often difficult for people with cancer to make decisions for their care. The aim of this review is to understand the importance of shared decisionmaking (SDM) in Indian clinical scenario and identify the gaps when compared to practices in the Western world. A systematic search (2000-2019) was executed in Medline and Google Scholar using predefined keywords. Of the approximate 400 articles retrieved, 43 articles (Indian: 5; Western: 38) were selected for literature review. Literature review revealed the paucity of information on SDM in India compared to the Western world data. This may contribute to patientreported physical or psychological harms, life disruptions, or unnecessary financial costs. Western world data demonstrate the involvement and sharing of information by both patient and physician, collective efforts of the two to build consensus for preferred treatment. In India, involvement of patients in the planning for treatment is largely limited to tertiary care centers, academic institutes, or only when the cost of therapy is high. In addition, cultural beliefs and prejudices impact the extent of participation and engagement of a patient in disease management. Communication failures have been found to strongly correlate with the medicolegal malpractice litigations. Research is needed to explore ways to how to incorporate SDM into routine oncology practice. India has a high unmet need towards SDM in diagnosis and treatment of cancer. Physicians need to involve patients or their immediate family members in decision making, to make it a patient-centric approach as well. SDM enforces to avoid uninformed decisionmaking or a lack of trust in the treating physician's knowledge and skills. Physician and patient education, development of tools and guiding policies, widespread implementation, and periodic assessments may advance the practice of SDM.

Ki-67 labeling index as a predictor of response to neoadjuvant chemotherapy in breast cancer.

AIMS: To investigate Ki-67 index with regard to its ability to predict achievement of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer patient. MATERIAL AND METHODS: It was a prospective observational study, conducted in Department of Medical Oncology, Rajiv Gandhi Cancer Institute & Research Center (RGCIRC), New Delhi from February 2014 to March 2016. A total of 134 patients with Stage II/III breast cancer who underwent NACT followed by surgery at our center were enrolled and analyzed. Before starting the treatment, clinical, tumor-related and treatment-related factors were recorded. Response evaluation was done clinically and radiologically after completion of NACT and pathologically on the surgical specimen. We calculated Ki-67 cut-off of 35% to label it as high by area under Receiver operating characteristic curve analysis for prediction of pCR. RESULTS: Clinical complete response (cCR) was observed in 35/134 (26.1%) patients while pCR was observed in 32/134 (23.9%) patients. On univariate analysis, higher grade (III), high Ki-67 index (>35%) and number of chemotherapy cycles (>3) were associated with better CCR rates. On multivariate analysis, number of chemotherapy cycles (>3) and high Ki-67 index (>35%) were independent predictive factors. For the predictive factors of pCR, univariate analysis showed grade (III), estrogen receptor/progesterone receptor negativity, HER-2 positivity, number of chemotherapy cycles (>3), TNBC and high Ki-67 index (>35%) to be associated with higher pCR rates. On multivariate analysis, Ki-67 index >35% and HER-2 positivity were the only independent predictive factors of pCR. CONCLUSIONS: We suggest 35% as best cut-off for Ki-67 expression for predicting response to NACT and achievement of pCR. Validation of this cut-off is required in larger studies.

Risk stratification and staging in prostate cancer with prostatic specific membrane antigen PET/CTObjective: A one-stop-shop.

OBJECTIVE: Current imaging modalities for prostate cancer (PC) had limitations for risk stratification and staging. Magnetic resonance imaging (MRI) frequently underestimated lymphatic metastasis while bone scintigraphy often had diagnostic dilemmas. Prostatic specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has been remarkable in diagnosing PC recurrence and staging. We hypothesized it can become one-stop-shop for initial risk stratification and staging. SUBJECTS AND METHOD: Ninety seven PSMA PET-CT studies were re analysed for tumor node metastases (TNM) staging and risk stratification of lymphatic and distant metastases proportion. The histopathology of 23/97 patients was available as gold standard. Chi-square test was used for proportion comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), over-estimation, under-estimation and correct-estimation of T and N stages were calculated. Cohen's kappa coefficient (k) was derived for inter-rater agreement. RESULTS: Lymphic or distant metastases detection on PSMA PET/CT increased significantly with increase in risk category. PSMA PET/CT sensitivity, specificity, PPV and NPV for extra prostatic extension (EPE), seminal vesicle invasion (SVI) and lymphatic metastases were 63.16%, 100%, 100%, 36.36% & 55%, 100%, 100%, 25% and 65.62%, 99.31%, 87.50%, 97.53%, respectively. Cohen's kappa coefficient showed substantial agreement between PSMA PET/CT and histopathological lymphic metastases (κ 0.734) however, it was just in fair agreement (κ 0.277) with T stage. PSMA PET/CT over-estimated, under-estimated and correct-estimated T and N stages in 8.71%, 39.13%, 52.17% and 8.71%, 4.35%, 86.96% cases, respectively. CONCLUSION: We found that PSMA PET/CT has potential for initial risk stratifications with reasonable correct estimation for N stage. However, it can underestimate T stage. Hence, we suggest that PSMA PET/CT should be used for staging and initial risk stratification of PC as one-stop-shop with regional MRI in surgically resectable cases.

FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients.

OBJECTIVE: There is no standard second-line chemotherapy after progression on first-line therapy including gemcitabine and platinum combination in advanced gall bladder cancer patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. METHODS: In this observational study, patients with performance status ≤2, who progressed on first-line therapy, were enrolled from May 2010 to June 2014. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. RESULTS: A total of 66 patients were enrolled in this study. The median age of patients was 52.5 years (32-66 years),of which 24 (36.36%) were males and 42 (63.63%) were females. The median number of cycles could be given were 9.5 (2-12). Only 43.93% patients in this study completed full 12 cycles of chemotherapy. Sixteen patients (24.24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 39 (59.09%) patients, with complete response in none, partial response in 16 (24.24%), stable disease in 23 (34.84%) and progressive disease in 27 (40.90%) patients. The median progression free survival was 3.9 months; median overall survival was 7.6 months. The main Grade 3/4 side effects seen were hematological in 31.81% (n = 21) and gastrointestinal in 25.75% (n = 17) patients. Majority of patients (46%) had Grade 1/2 peripheral neuropathy. CONCLUSIONS: FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment in advanced gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent.

A Prospective Evaluation of Symptom Prevalence and Overall Symptom Burden Among Cohort of Critically Ill Cancer Patients.

BACKGROUND: Gross physiological perturbations necessitating the Intensive Care Unit (ICU) admission might exacerbate the already existing or initiate bothersome symptoms among cancer patients. There is a lack of conclusive evidence concerning the symptomatic experience among this subgroup of cancer patients particularly so in the Indian population. The aim of this prospective observational study was to elucidate the symptom prevalence and overall symptomatic distress among critically ill cancer patients at the time of admission to a medical ICU. METHODS: We prospectively evaluated 110 consecutive cancer patients at the time of admission to our medical ICU for the presence and intensity of symptoms using a modified Edmonton Symptom Assessment Scale (ESAS). The patients/caregivers were also enquired regarding the most bothersome symptom in the past 1 week and the presence of "symptom associated sleep disturbance." The primary outcome was the prevalence of patients with moderate (ESAS ≥ 40) and severe (ESAS ≥ 70) symptomatic distress. RESULTS: The average age was 52.49 years with 75.45% of the respondents in the economically productive age group (21-60 years). Carcinoma breast (19.35%) and lung (14.58%) were the most common cancers among females and males, respectively. 87.27% and 60% of the patients had advanced cancer and multi-organ dysfunction, respectively. About 76.36% patients were able to complete ESAS either by themselves or with caregiver's assistance within first 24 h of ICU admission. The mean ESAS distress score was 48.04 (0-81) with 72.72% of the patients having moderate-severe symptomatic distress. Loss of appetite (92.73%) and nausea (54.55%) were the most common and the least common reported symptoms, respectively. Pain was the most common and "most distressing symptom" reported by 40% of patients with 64.55% patients reporting one or more symptoms severe enough to interfere with their sleep. CONCLUSION: ESAS is a user-friendly cognitive aid to make the healthcare team cognizant of the symptom existence and overall symptomatic burden among cancer patients with gross physiological perturbations. The high prevalence of moderate-severe symptom distress requires the concomitant provision of palliative and intensive care among this group of cancer patients.

The Prevalence and Characteristics of Pain in Critically Ill Cancer Patients: A Prospective Nonrandomized Observational Study.

CONTEXT: Pain is a distressing symptom common to all stages and ubiquitous at all levels of care in cancer patients. However, there is a lack of scientific literature on prevalence, severity, predictors, and the quality of pain in cancer patients admitted to an Intensive Care Unit (ICU). OBJECTIVES: To elucidate the prevalence of pain, moderate to severe pain, neuropathic pain, chronic pain, and pain as the most distressing symptom in critically ill-cancer patients at the time of ICU admission. METHODS: We prospectively interviewed 126 patients within first 24 h of admission to a medical ICU. The patients were assessed for the presence of pain, its severity, sites, duration, nature, and its impact as a distressing symptom. Numerical Rating Scale and self-report version of Leeds Assessment of Neuropathic Signs and Symptoms were used to elucidate intensity of pain and neuropathic pain, respectively. Demographic characteristics such as age and sex, primary site, and stage of cancer were considered for a possible correlation with the prevalence of pain. RESULTS: Of 126 patients included in the study 95 (75.40%), 79 (62.70%), 34 (26.98%), and 17 (13.49%) patients had pain, moderate-severe, chronic, and neuropathic pain, respectively. The average duration of pain was 171.16 ± 716.50 days. Totally, 58 (46.03%) and 42 (42.01%) patients had at least one and more than equal to 2 neuropathic pain symptoms, respectively. The primary malignancies associated with the highest prevalence of pain were genitourinary, hematological, and head and neck whereas breast and lung cancers were associated with the highest prevalence of neuropathic and chronic pain, respectively. CONCLUSION: The prevalence of pain among critically ill-cancer patients is high. Assessment for pain at the time of ICU admission would ensure appropriate assessment for the presence, type, severity, and the significance imparted to it.

Synchronous Triple Malignancy of Esophagus, Pancreas, and Pyriform Sinus: A Prima Facie Report.

The occurrence of triple synchronous primary malignant neoplasms is very rare. With improved cancer detection rates, widespread screening techniques and their availability, and improved general awareness, there has been a rise in the detection rate of patients with multiple primaries. Most of these cases consist of dual synchronous malignancies. However, triple synchronous malignancies have been reported and are extremely rare in literature. In such cases, the etiology is unknown most of the time, and management of such a situation remains challenging. We report such a case in a 71-year-old male with no genetic predisposition or family history of malignancy, presenting with three primary malignancies of the buccal mucosa, esophagus, and pancreas. Investigations revealed three histologically separate tumors in the buccal mucosa, esophagus, and pancreas. The patient was treated initially with a first-line combination of chemotherapy and later with a 2nd-line palliative chemotherapy. The prognosis of such patients is poor. Our patient is still on 2nd-line palliative chemotherapy without any major complications.

Practical Consensus Guidelines for the Use of S-1 in GI Malignancies.

Purvish M ParikhS-1 (5-fluorouracil prodrug [tegafur] in combination with 5-chloro-2,4-dihydroxypyridine [CDHP] and potassium oxonate [OXO]) was first approved in 1999. In order to make it easy for community oncologists, we decided to put together this expert consensus guideline for its use in gastrointestinal (GI) malignancies. A total of 15 subject matter experts used modified Delphi method to discuss, analyze, and vote on key aspects regarding practical approach to use of S-1 in GI cancers, a process involving 6 months of work. The consensus guidelines specify how S-1 use can be optimized in patients with colorectal, gastric, and pancreatic tumors. The voting for the 17 key points resulted in a majority consensus for all the statements (approval ranging from 13/15 [87%] to 15/15 [100%]). S-1 is a combination of three drugs (tegafur, CDHP, and OXO) specifically designed to reduce toxicity and enhance efficacy; clinical data and meta-analysis confirm both factors; and it is recommended as standard of care for GI cancers. S-1 is approved and one of the standards of care for all lines of therapy in colorectal cancer and pancreatic cancers. S-1 with oxaliplatin is the standard of care for gastric cancers.

Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A single center study.

BACKGROUND: Adenocarcinoma, a subgroup of non-small cell lung cancer, is the most frequent form occurring in the non-smokers. Mutation in tyrosine kinase domain of epidermal growth factor receptor (EGFR) has been a common feature observed in lung adenocarcinoma. The study was carried out to detect the prevalence of EGFR mutation in lung adenocarcinoma. MATERIALS AND METHODS: EGFR mutation status in 166 lung adenocarcinoma patients was obtained retrospectively. Mutation tests were performed on paraffin embedded tissue blocks as a routine diagnostic procedure by polymerase chain reaction followed by direct nucleotide sequencing. Patient's demographics and other clinical details were obtained from the medical records. RESULTS: EGFR mutation was detected in 43/166 (25.9%) patients. Gender wise mutation was observed as 18/55 (32.7%) in females and 25/111 (22.5%) in males. Overall, EGFR mutation was correlated with never smokers and distant metastasis (P < 0.05), but not associated with the gender, disease stage and pleural effusion. Exon 19 deletions were significantly correlated with females, never smokers, pleural effusion and distant metastasis (P < 0.05). However, point mutation on exon 21 did not show any statistical association with the above variables. Median overall survival was 22 months (95% confidence interval, 15.4-28.6). Female sex, EGFR mutation and absence of metastasis are associated with good prognosis. CONCLUSION: EGFR mutation in lung adenocarcinoma was higher in never smokers, females and patients with distant metastasis. However, it was not linked with tobacco smoking. The prevalence of EGFR mutation observed is in range with the previously published reports from the Asian countries.

Interaortocaval Lymph Node Metastasis in Gall Bladder Cancer: Is It Regional Node or Metastatic Disease?

BACKGROUND AND OBJECTIVES: Interaortocaval or para-aortic lymph node (IACLN) metastasis in gall bladder cancer (GBC) is usually a contraindication to curative resection with a prognosis similar to liver or peritoneal metastases. However, few authors have reported survival similar to regional lymph node (RLN) positive disease after curative resection in these patients. This study aims to analyse the role of curative surgery in such cases. METHODS: Data of all patients operated for GBC from 2012 to 2019 was retrieved. Survival of the IACLN- and RLN-positive patients was compared and factors associated with recurrence and survival were analysed. RESULTS: Patients were divided in RLN-positive (n = 47) and IACLN-positive (n = 17) group. At a median follow-up of 19.7 months, median disease-free survival (18 vs 13 months) and median overall survival (27 vs 20 months) were inferior (p = 0.06) in IACLN group. But it was higher than the patients who received only palliative therapy (median OS, 14 months). Lack of adjuvant therapy was a significant factor for disease recurrence. CONCLUSION: Selected cases of GBC with IACLN metastases can achieve meaningful survival after curative resection and adjuvant therapy. Survival was inferior to RLN-positive cases but it was higher than the patients who received only palliative chemotherapy. This concept needs further evaluation in a prospective study with larger number of patients.

Study of Efficacy and Toxicity of Capecitabine Maintenance After Response to Docetaxel, Cisplatin, and 5-Fluracil-Based Chemotherapy in Advanced Carcinoma Stomach.

BACKGROUND: Advanced gastric cancer is associated with poor survival despite chemotherapy. Maintenance chemotherapy has been successfully tried in lung cancer and colorectal cancers however there is scarce literature on maintenance therapy in advanced gastric cancer. We report a prospective non-randomized single-arm trial of capecitabine maintenance after response to docetaxel, cisplatin, and 5-Flurouracil-based chemotherapy. METHODS: 50 patients with advanced gastric cancer, who had achieved response or had stable disease after 6 cycles of Docetaxel, Cisplatin, and 5-Flurouracil (D 75 mg/m2, C 75 mg/m2, FU 750 mg/m2/d d1-d5, q3 weeks) chemotherapy were prospectively selected to receive maintenance chemotherapy with capecitabine (1000mg/ m2 bid d1-d14 q21 days) until progression. RESULTS: During the median follow-up period of 18 months all patients had progressed, however, there was no treatment-related death, the median time to tumor progression was 10.3 months, with grade 3 and 4 toxicities in 10-15% of patients, and treatment delays in 75% of patients. CONCLUSIONS: Our study has shown that maintenance chemotherapy with capecitabine post-first-line docetaxel, cisplatin, and 5-FU-based chemotherapy is effective and delays tumor progression. However, toxicity was a concern in our study which led to treatment-related delays but without any treatment-related death. Most patients continued therapy till progression.

2/1 dose schedule of sunitinib is superior than the 4/2 regimen for the first-line therapy of clear cell metastatic renal cell carcinoma - An Indian experience.

BACKGROUND: Sunitinib remains the first-line treatment for favorable risk metastatic clear cell renal cell cancer (mccRCC). It was conventionally given in the 4/2 schedule; however, toxicity necessitated trying the 2/1 regimen. Regional variations in treatment response and toxicity are known, and there is no data from the Indian subcontinent about the outcomes of the alternative dosing schedule. METHODS: Clinical records of all consecutive adult patients who received sunitinib as first-line therapy for histologically proven mccRCC following cytoreductive nephrectomy from 2010-2018 were reviewed. The primary objective was to determine the progression-free survival (PFS), and the secondary objectives were to evaluate the response rate (objective response rate and clinical benefit rate), toxicity, and overall survival. A list of variables having a biologically plausible association with outcome was drawn and multivariate inverse probability treatment weights (IPTW) analysis was done to determine the absolute effect size of dosing schedules on PFS in terms of "average treatment effect on the treated" and "potential outcome mean." RESULTS: We found 2/1 schedule to be independently associated with higher PFS on IPTW analysis such that if every patient in the subpopulation received sunitinib by the 2/1 schedule, the average time to progression was estimated to be higher by 6.1 months than the 4/2 schedule. We also found 2/1 group to have a lower incidence than the 4/2 group for nearly all ≥ grade 3 adverse effects. Other secondary outcomes were comparable between both treatment groups. CONCLUSION: Sunitinib should be given via the 2/1 schedule in Indian patients.

Survival and Recurrence Patterns in Patients With Stomach Adenocarcinoma Receiving Chemotherapy or Chemoradiotherapy After D2 Gastrectomy in a Tertiary Care Cancer Institute: A Retrospective Real-World Evidence Cohort Study.

Purpose: Clinical trials comparing the efficacy of adjuvant chemotherapy (CT) and chemo radiation therapy (CTRT) for stomach adenocarcinoma have reported equivocal results. Hence, the current retrospective cohort study assessed the long-term survival and recurrence outcomes of these therapies, to generate evidence in a real-world scenario. Methods and Materials: Pathologically confirmed patients with stomach adenocarcinoma aged ≥18 years who underwent gastrectomy and D2 lymph nodal dissection at a tertiary cancer hospital from January 2010 to October 2017 were enrolled. Hospital-based follow-up was performed until December 2021. Data were gathered from electronic medical records, supplemented by telephonic interviews for patients who could not come for physical follow-up. CT-alone and CTRT cohorts were compared in terms of survival and recurrence outcomes. Results: The analysis included 158 patients (mean age, 56.42 years; 63.9% male; CT-alone cohort, 69; CTRT cohort, 89). Patients in the CTRT cohort had significantly worse tumor characteristics at baseline (29.2% had the diffuse type of tumor, 94.4% had stage II or III, 68.5% had lympho-vascular space invasion, and 85.4% had lymph node involvement). Recurrence was observed in 13 (19.7%) of the 76 followed-up patients. Although locoregional recurrence was higher in the CT-alone cohort (7 vs 2), distant metastasis was higher in the CTRT cohort (3 vs 1). The overall 5-year survival was 67.0% (SE, 5.0%) and 5-year recurrence-free survival (RFS) was 75.0% (SE, 5.0%). On multivariate Cox regression, no variable was significantly associated with the overall survival, whereas age, positive lymph nodes without extracapsular extension, and lymph node-negative were significantly associated with RFS. The CTRT cohort had significantly (84.0%) higher RFS (hazard ratio, 0.161; 95% CI, 0.056-0.464; P < .001). Conclusions: Patients who received adjuvant CTRT after D2 dissection showed similar overall survival but significantly higher RFS than the CT-alone cohort, despite having worse baseline tumor characteristics.

Survival of Trial-Like and Non-Trial-Like Patients With Immunotherapy in Advanced Hepatocellular Carcinoma in Real World: A Collaborative Multicenter Indian Study (IMHEP).

PURPOSE: Immune checkpoint inhibitors (ICIs) is the initial line of management in advanced hepatocellular carcinoma (HCC), but survivals in the real world are not known. MATERIALS AND METHODS: A retrospective study of patients with advanced HCC receiving ICIs (as first-line therapy or as later lines of therapy) across 11 Indian institutions was conducted. Patients were divided into either cohort 1 (trial-like receiving ICI as first-line therapy), with a Child Pugh score (CTP) of ≤6, an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1, and no VP4 (main portal vein thrombosis [MPVT]) or cohort 2 (trial unlike) who did not satisfy at least one of the above criteria. The primary end point was 12-month overall survival (OS). RESULTS: Between January 2017 and January 2022, 133 patient data were analyzed. The presence of MPVT was seen in 33 patients (25%). The ICIs used were atezolizumab-bevacizumab, nivolumab, and pembrolizumab in 89 (66%), 44 (33%), and one (1%) patients, respectively. With a median follow-up of 13.8 months, the 12-month OS for the entire cohort was 33.4% (95% CI, 23.6 to 43.2). Patients in cohort 1 (n = 31) had a significantly improved OS compared with patients in cohort 2 (n = 102; 12-month OS, 57.9% [95% CI, 38.5 to 77.3] v 24% [95% CI, 13.4 to 34.6]; P = .005). Patients with CTP A as compared with CTP B (9.7 v 4.3 months; P < .001) and an ECOG PS of 0/1 as compared with a PS of ≥2 (8.7 v 7.2 months; P = .04) and without MPVT (9.4 v 4.0; P < .001) had superior survivals. CONCLUSION: Patients with advanced HCC in the real world, trial-like have survivals in consonance with trial data, whereas patients with features excluding them from trials, such as main portal vein thrombosis, poor ECOG PS, and child Pugh B status, have markedly inferior survivals, despite good tolerance to immunotherapy.

Practice Patterns and Survival in Patients with Resected Pancreatic Ductal Adenocarcinomas (PDAC) - Results from the Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) Study.

BACKGROUND: There is limited data from India with regard to presentation, practice patterns and survivals in resected pancreatic ductal adenocarcinomas (PDACs). METHODS: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) included data from 8 major academic institutions across India and presents the outcomes in upfront resected PDACs from January 2015 to June 2019. RESULTS: Of 288 patients, R0 resection was achieved in 81% and adjuvant therapy was administered in 75% of patients. With a median follow-up of 42 months (95% CI: 39-45), median DFS for the entire cohort was 39 months (95% CI: 25.4-52.5), and median overall survival (OS) was 45 months (95% CI: 32.3-57.7). A separate analysis was done in which patients were divided into 3 groups: (a) those with stage I and absent PNI (SI&PNI-), (b) those with either stage II/III OR presence of PNI (SII/III/PNI+), and (c) those with stage II/III AND presence of PNI (SII/III&PNI+). The DFS was significantly lesser in patients with SII/III&PNI+ (median 25, 95% CI: 14.1-35.9 months), compared to SII/III/PNI + (median 40, 95% CI: 24-55 months) and SI&PNI- (median, not reached) (p = 0.036)). CONCLUSIONS: The MIPPAP study shows that resectable PDACs in India have survivals at par with previously published data. Adjuvant therapy was administered in 75% patients. Adjuvant radiotherapy does not seem to add to survival after R0 resection.

BRCA mutations: Implications of genetic testing in ovarian cancer.

Ovarian cancer (OC) is one of the most lethal gynecological cancers with a 5-year survival rate that ranges from 30% to 40%. Breast cancer genes (BRCA1 and BRCA2) play a key role in maintaining genomic stability. Mutations in BRCA1/2 genes lead to the accumulation of double-strand breaks, resulting in tumorigenesis. The risk of developing OC in women with BRCA1 and BRCA2 mutations is 39% and 11%, respectively, by 70 years of age. BRCA1/2 mutation testing is thus important to identify women at greatest risk of developing OC in addition to its impact on diagnosis, prognosis, and targeted therapy. Genetic testing is required to identify the BRCA mutations and thus select patients who can benefit from polyadenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitor therapy. Tumor BRCA mutation testing can detect both germline and somatic mutations allowing implementation of preventive strategies on a broader population. Various international guidelines recommend BRCA1/2 mutation genetic testing in all OC patients irrespective of age and family history. This review focuses on the role of BRCA mutation testing in OC.

First-line chemotherapy analysis on survival in carcinoma ovary patients: Data from a Northern Indian cancer center.

Aims: This study aims to assess the survival and identify the prognostic factors in ovarian cancer patients treated with surgery and carboplatin/paclitaxel based first-line chemotherapy (CT). Settings and Design: The electronic medical records of all ovarian cancer patients registered during January 2009 and December 2017 were screened retrospectively. Subjects and Methods: A total of 440 cases were included in accordance with the inclusion/exclusion criteria of study. The comprehensive data regarding demography, treatment, chemotoxicities, recurrence, and others were collated and analyzed. Statistical Analysis Used: Cox regression analysis was used for univariate and multivariate analyses of prognostic factors. Results: The median age at diagnosis was 50.6 years. All cases had got CT-related morbidity but no associated mortality. The median recurrence-free survival (RFS) and mean overall survival (OS) were 30 (95% confidence interval [CI]: 24.65-35.38) months and 40.4 months, respectively. A significant difference was observed among the RFS (P < 0.001); and OS (P = 0.036) in relation to the stage of disease. Furthermore, patients who relapsed post first-line CT had 36%, 9%, 3% recurrence in second-, third-, and fourth-line CT regimens, respectively. Multivariate analysis proved the histology, low-grade serous, to be the favorable prognostic factor for RFS (hazard ratio = 0.18; 95% CI: 0.04-0.82). Conclusions: Surgery and first-line CT with carboplatin/paclitaxel lead-to-moderate long-term survival in ovarian cancer. The likelihood of relapse is fairly high as stage advances. Low-grade serous histology is an independent prognostic factor for RFS.

Analysis of Spatial Heterogeneity of Responses in Metastatic Sites in Renal Cell Carcinoma Patients Treated with Nivolumab.

Background: The purpose was to determine whether tumor response to CPI varies by organ and to characterize response patterns in a group of surgically treated metastatic RCC patients treated with Nivolumab. Methods: A retrospective analysis was undertaken between January 2016 and March 2020 on patients receiving Nivolumab for metastatic RCC, following first-line therapy and having at least one baseline and two follow-up scans. A Fisher's exact test was used to compare categorical variables, and a Kruskal-Wallis test was used to compare continuous variables. Results: Twenty-one out of thirty patients evaluated were eligible, and they were divided into two groups: responders (n = 11) and non-responders (n = 10). According to all iRECIST standards, 18 (85.7 percent) of the 21 patients had PD (10 patients), PR (3 patients), or SD (8 patients). At baseline, 7, 15, 4, 13, 7, and 7 patients, respectively, had detectable hepatic metastasis and lung, brain, lymph node, soft tissue, and other intra-abdominal metastases; these patients were evaluated for organ-specific response. The ORRs for hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals, and other intraperitoneal metastases were correspondingly 10%, 20%, 35%, 0%, and 25%. In total, 13 (61.9%) of them demonstrated varied responses to CPI therapy, with 6 (28.5%) demonstrating intra-organ differential responses. The lymph nodes (35%) had the best objective response (BOR), followed by the adrenals and peritoneum (both 25%), the brain (20%), and the lung (20%). The response rate was highest in adrenal gland lesions (2/4; 50%), followed by lymph nodes (13/19; 68.4 percent) and liver (5/10; 50%), whereas rates were lowest for lesions in the lung (9/25; 36%), intraperitoneal metastases (1/4; 25%), and brain (1/5; 20%). Conclusions: In renal cell carcinoma, checkpoint inhibitors have a variable response at different metastatic sites, with the best response occurring in lymph nodes and the least occurring in soft tissue.