ExPert ConsEnsus on the management of Advanced clear-cell RenaL celL carcinoma: INDIAn Perspective (PEARL-INDIA).

In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological (IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.

Effect of age, comorbidity and remission status on outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. METHODS: Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. RESULTS: Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7-49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age < 60 years (p = 0.05). CONCLUSIONS: Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.

Hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: A single institution Indian experience.

BACKGROUND: Cytoreductive surgery followed by hyper- thermic intraperitoneal chemotherapy (HIPEC) has shown better oncological outcomes in peritoneal surface malignancies (PSM). We assessed the feasibility and perioperative outcomes of this procedure in Indian patients. METHODS: In this prospective observational study from February 2013 to April 2015, we included 56 patients (41 females, 73.2%) with PSM. They had a good performance status, were either treatment-naïve or previously treated by surgery and systemic chemotherapy. They underwent cytoreductive surgery followed by HIPEC using a hyperthermia pump, with the temperature at 42 °C for 30-90 minutes. The chemotherapy regimen was based on the primary malignancy. Perioperative outcome data were collected and analysed. We also analysed the short-term oncological outcomes. RESULTS: Our patients included those with peritoneum confined ovarian carcinoma (32, 57.1%), colorectal carcinoma (9, 16.1%), pseudomyxoma peritonei (7, 12.5%), meso- thelioma (2, 3.6%), gastric carcinoma (2, 3.6%) and others (4, 7.1%). The median duration of surgery including HIPEC was 9 hours and the median hospital stay was 12 days. The median time for gastrointestinal recovery was 5 days. One-fifth of patients (11, 19.7%) required an extended stay in the inten- sive care unit. The most common grades 3 and 4 complications were hypocalcaemia 32.1%, hypokalaemia 32.1%, anaemia 21.4% and thrombocytopenia 7.1%. Major morbidity requiring surgical intervention occurred in 8.9% of patients. The 60-day operative mortality was 1.8%. At a median follow-up of 16 months, 7.1% developed peritoneal recurrence, 8.9% had systemic recurrence and 7.1% succumbed to the disease. Patients with platinum-resistant ovarian carcinomas had more peritoneal recurrence (3.6%). CONCLUSION: In patients with PSM, surgical cytoreduction and HIPEC is feasible and potentially beneficial. It can be done with low mortality and acceptable morbidity. It requires a dedicated team of surgeons, anaesthetists and intensivists and proper infrastructure.

Molecular Testing in Stage 4 Stomach Cancer in India: A Single-Centre Experience.

Introduction Advanced gastric cancer (GC) has a very poor prognosis, and chemotherapy has been the standard of care. The use of immunotherapy or targeted therapy in the stage 4 setting is dependent on molecular testing of the tumour. There is a paucity of data in the Indian scenario on testing for molecular markers in stage 4 GC. Therefore, in this study, we looked at the prevalence of human epidermal growth factor receptor 2 (HER2/neu) expression/amplification, deficient mismatch repair (d-MMR)/microsatellite instability (MSI) high status, and programmed death ligand 1 (PDL-1) status in stage 4 gastric/gastroesophageal junction (GEJ) adenocarcinoma. Methods A retrospective single-centre observational study was conducted between January 2017 and January 2022 of patients diagnosed with stage 4 GC/GEJ adenocarcinoma. Patient data were collected from stored electronic patient records. Data on stage 4 patients who underwent testing for HER2/neu, mismatch repair (MMR)/MSI, and PDL-1 status were recorded. Treatment received was also noted. Results During the study period, 139 patients were diagnosed with stage 4 GC/GEJ adenocarcinoma. HER2/neu testing was done in 99 stage 4 patients (71.2%), with a positivity rate of 16.16% (n = 16). All patients diagnosed as HER2/neu-positive were treated with trastuzumab. Testing of MMR status was carried out in 91 stage 4 patients (65.4%). d-MMR/MSI high was detected in eight patients (8.8%), of which germline MMR was detected as positive in one patient. Five of these eight patients (62.5%) received immune checkpoint inhibitors. PDL-1 testing was done in 61 of the 139 stage 4 patients (43.9%). Twenty patients (32.7%) had PDL-1 tumour proportion score > 1%/combined positive score > 1. Conclusion Molecular profiling has now become the standard while treating late-stage GC. HER2/neu-positive patients have improved survival due to the use of anti-HER2/neu-targeted therapies. It is important to look at not only PDL-1 but also MMR to identify patients who would be eligible and benefit from immunotherapy.

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.

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.

Evolving trends in lung cancer: Epidemiology, diagnosis, and management.

Lung cancer is one of the deadliest cancers globally and accounts for most of the cancer-related deaths in India. Comprehensive data on lung cancer in India are lacking. This review aimed to discuss the epidemiological trends of lung cancers and driver mutations as well as the recent advancements in molecular diagnostics and therapeutic options primarily in non-small cell lung cancer (NSCLC) in India. Electronic databases, such as PubMed and Google Scholar, were searched to retrieve the relevant literature published in the past 5 years. As per the GLOBOCAN 2018 report, lung cancer was ranked the fourth leading cause of cancer (5.9% cases) in India, in all ages and sexes. Furthermore, 63,475 of all cancer-related deaths (8.1%) were attributed to lung cancer (cumulative risk 0.60), making it the third leading cause of cancer-related mortality. The common mutations that have been detected and targeted for treatment in lung cancer patients include EGFR, ALK, and PD-L1. In India, EGFR and ALK mutations are commonly reported, but not PD-L1 mutation. Molecular testing has gained importance as several biomarkers are being targeted to diagnose lung cancer patients. Surgery, radiotherapy, systemic chemotherapy, and personalized molecular-targeted therapy prolong the overall survival (OS) in patients with NSCLC. Although chemotherapy and molecular-targeted therapies have greatly improved the clinical outcomes, prolonged disease control could not be attained in most NSCLC patients. In this situation, immunotherapy seems to be potentially beneficial to obtain long-lasting disease control with minimal adverse events or safety concerns.

Maintenance therapy for newly diagnosed epithelial ovarian cancer- a review.

Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer among women worldwide, with the 5-year survival rate ranging between 30 and 40%. Due to the asymptomatic nature of the condition, it is more likely to be diagnosed at an advanced stage, requiring an aggressive therapeutic approach. Cytoreductive surgery (CRS) along with systemic chemotherapy with paclitaxel and carboplatin has been the mainstay of the treatment in the frontline management of EOC. In recent years, neo-adjuvant chemotherapy, followed by interval CRS has become an important strategy for the management of advanced EOC. Due to the high rate of recurrence, the oncology community has begun to shift its focus to molecular-targeted agents and maintenance therapy in the frontline settings. The rationale for maintenance therapy is to delay the progression or relapse of the disease, as long as possible after first-line treatment, irrespective of the amount of residual disease. Tumours with homologous recombination deficiency (HRD) including BReast CAncer gene (BRCA) mutations are found to be sensitive to polyadenosine diphosphate-ribose polymerase (PARP) inhibitors and understanding of HRD status has become important in the frontline setting. PARP inhibitors are reported to provide a significant improvement in progression-free survival and have an acceptable safety profile. PARP inhibitors have also been found to act regardless of BRCA status. Recently, PARP inhibitors as maintenance therapy in the frontline settings showed encouraging results in EOC; however, the results from further trials and survival data from ongoing trials are awaited for understanding the role of this pathway in treatment of EOC. This review discusses an overview of maintenance strategies in newly diagnosed EOC along with considerations for maintenance therapy in EOC with a focus on PARP inhibitors.

Real-World Experience with Nivolumab in Metastatic Renal Cell Carcinoma Patients Who Have Progressed on Prior Therapies: A Single-Center Study from India.

Amit RauthanIntroduction Nivolumab monotherapy is approved for the treatment of metastatic renal cell carcinoma (mRCC) patients who have progressed on prior therapies based on the pivotal Checkmate-025 trial. There is limited literature on the efficacy and safety profile of usage of nivolumab in the treatment of mRCC in India in a real-world setting. Methods A retrospective analysis was performed of patients who received nivolumab monotherapy for mRCC after having progressed on prior therapies. Tumor response was graded according to RECIST v1.1 and Kaplan-Meier survival analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Immune-related adverse events (irAEs) were documented and graded according to CTCAE v5.0. Results Between 2016 and 2019, 35 patients received nivolumab for mRCC at our center after progression on prior therapies. A majority of the patients ( n = 30, 85.7%) received it in a second-line setting, and the remaining in the third line and beyond setting. Clear cell was the most common histology ( n = 26, 74.3%). There were 18 patients (51.42%) who belonged to IMDC intermediate risk, while 17 (48.58%) patients were at poor risk. The overall response rate was 60%, with complete response (CR) in 11.4%. Median duration of response was not reached among responders. Median PFS was 5 months (95% confidence interval [CI]: 3.06-6.93) and median OS was 26 months (95% CI: 1.90-50.09). Ongoing survival of 47, 42, 34, and 22 months was noted in four patients with CR, respectively. In our study, 23 patients (65.71%) experienced any grade of irAE. Grade 3 irAEs was seen in four patients (11.42%). Most common irAE was thyroid dysfunction seen in 12 patients (34.2%). Treatment discontinuation due to irAEs occurred in three patients (8.57%). Conclusion Nivolumab showed good efficacy with high response rates and an OS comparable to the pivotal Checkmate-025 trial. It was well tolerated with safety profile in terms of irAE consistent with those reported in literature.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer with Peritoneal Metastasis-Indian Experience.

Ashwin K.R.Introduction Peritoneal metastasis secondary to gastric cancer is associated with poor prognosis. Recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may be an efficacious treatment option for an otherwise palliative condition. Methods A retrospective single institutional study of patents diagnosed with gastric carcinoma and peritoneal metastasis and treated with CRS and HIPEC from February 2015 to December 2019. Results Sixteen patients with gastric cancer and peritoneal carcinomatosis were treated with CRS and HIPEC. Three patients underwent upfront surgery, and five patients underwent interval surgery. The mean peritoneal cancer index (PCI) was 3.5, and adequate complete cytoreduction (CC) score of 0/1 was achieved in all patients. All patients received HIPEC with mitomycin C. Major surgical complications were in 12.5% of patients. Grade I surgical site infection was present in one patient. Three patients had prolonged gastrointestinal (GI) recovery. The 30-day mortality was zero. Median follow-up time was 39 months. The median progression-free survival (PFS) was 12 months (95% confidence interval [CI] 6.86-17.13). The median overall survival (OS) was 17 months (95% CI 6.36-27.64). Conclusion Multidisciplinary treatment of perioperative chemotherapy with CRS and HIPEC is a promising treatment option, which may prolong survival in selected patients, and large randomized clinical trials are warranted for it to become standard of care.

Mucormycosis of the Breast in a Patient With Breast Carcinoma After COVID-19 Pneumonia.

Mucormycosis is a rare, but potentially fatal, fungal infection which is caused by mucormyctes. These forms of fungi are typically known to infect immuno-compromised individuals but are rare in immunocompetent individuals. Herein, we report the case of a 52 year-old female who was diagnosed with right breast carcinoma in Manipal Hospital, a tertiary cancer care center. The patient was a known diabetic and hypertensive and who had recently recovered from coronavirus disease-2019 (COVID-19) pneumonia. In the due course of management, she developed mucormycosis infection at the operative site in her right breast where she had a radiation therapy-induced wound. This patient was successfully treated with an aggressive regimen of early surgical debridement along with administration of systemic amphotericin B.

An Overview of the Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy in Operable Breast Cancer in a Tertiary Care Centre in South India.

Objective: The incidence of female breast cancer in the world is 11.7% with a mortality rate of 6.9%. According to Globocon 2020, breast cancer is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer-related death amongst women worldwide. The purpose of this study was to analyze the impact of Body Mass Index (BMI) on pathological complete response (pCR) rates for operable breast cancer after neoadjuvant chemotherapy (NACT). The primary endpoint was to assess histopathological features of the surgical specimen in response to NACT and to investigate the relationship with pre-chemotherapy BMI taking into account the various molecular subtypes of breast cancer. Materials and Methods: Patients with biopsy-proven breast carcinoma who underwent surgery after NACT between January 2017 and May 2021 were included. All patients were initially divided into three groups depending on their pre-chemotherapy BMI. With BMI <22.9 as normal or underweight category, BMI of 23-27.4, was taken as overweight category and BMI ≥27.5 as obese category. Results: The study included 184 patients. Normal weight patients had the highest rate of pCR (75%) and the lowest was seen in the obese category (33.75%). Furthermore, the subtype most likely to achieve pCR was HER2+/ER negative followed by triple negative BC with odds ratios of 3.46 and 2.21, respectively. Conclusion: This retrospective study established that overweight and obese patients suffering from breast carcinoma had a lessened pCR rate following NACT in comparison with those who were under-/normal weight.

Toxicity profile of chemotherapy agents used in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

INTRODUCTION: Morbidity associated with cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is due to the synergistic effect of cytoreduction, effect hyperthermia and the cytotoxic agents used for HIPEC. This study was done to analyse the postoperative morbidity in relation to the chemotherapy agent used in patients undergoing CRS-HIPEC for peritoneal surface malignancy (PSM) in Indian set up. MATERIALS AND METHODS: Patient with PSM, underwent CRS-HIPEC as per the institutional protocol. Patients were stratified as per the chemotherapy drug used during HIPEC & perioperative outcome were documented. RESULTS: 163 patients underwent CRS-HIPEC for PSM: 67.4% were of ovarian primary. Others were colorectal, appendicular, gastric primary and rare tumors.Cisplatin was the most common drug used: as alone (57.05%) or in combination with Adriamycin (12.88%). Mitomycin-C (MMC) was used in 20% and oxaliplatin in 10%.Grade 3-5 morbidity in the whole cohort was 44.8% and grade 1-2 was 74%.Grade 1-2 electrolyte abnormality was the most common morbidity overall and grade 3-4 hematological toxicity was the most common severe morbidity. Frequency of grade 3-5 morbidity were 38.7%, 48.5%,50% and 61.9% for Cisplatin alone, MMC, oxaliplatin and Adriamycin + cisplatin respectively. None of the patients had grade 3-4 nephrotoxicity as sole complication. All major complications were highest in the group who received Adriamycin. Cisplatin was associated with higher rate of electrolyte imbalance, oxaliplatin with post-operative bleeding. Rates of other complications did not differ significantly. CONCLUSION: Cisplatin followed by MMC were the well tolerated drugs during HIPEC and tolerance to Adriamycin combination regimen in Indian patients was poor.

Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study.

BACKGROUND AIMS: Spinal cord injury (SCI) is a medically untreatable condition for which stem cells have created hope in the last few years. Earlier pre-clinical reports have shown that transplantation of bone marrow (BM) mesenchymal stromal cells (MSC) in SCI-simulated models can produce encouraging results. In a clinical pilot study, we investigated the growth kinetics of BM MSC from SCI patients, their safety and functional improvement post-transplantation. METHODS: Thirty patients with clinically complete SCI at cervical or thoracic levels were recruited and divided into two groups based on the duration of injury. Patients with <6 months of post-SCI were recruited into group 1 and patients with >6 months of post-SCI were included into group 2. Autologous BM was harvested from the iliac crest of SCI patients under local anesthesia and BM MSC were isolated and expanded ex vivo. BM MSC were tested for quality control, characterized for cell surface markers and transplanted back to the patient via lumbar puncture at a dose of 1 x 10(6) cells/kg body weight. RESULTS: At the time of writing, three patients had completed 3 years of follow-up post-BM MSC administration, 10 patients 2 years follow-up and 10 patients 1 year follow-up. Five patients have been lost to follow-up. None of the patients have reported any adverse events associated with BM MSC transplantation. CONCLUSIONS: The results indicate that our protocol is safe with no serious adverse events following transplantation in SCI patients. The number of patients recruited and the uncontrolled nature of the trial do not permit demonstration of the effectiveness of the treatment involved. However, the results encourage further trials with higher doses and different routes of administration in order to demonstrate the recovery/efficacy if any, in SCI patients.

Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives - a review.

Epithelial ovarian cancer (EOC) is usually diagnosed late at an advanced stage. Though EOC initially responds to treatment, the recurrence rate is pretty high. The efficacy of different targeted therapies reduces with each recurrence. Hence there is need of effective maintenance therapy in recurrent EOC. Recently, polyADP-ribose polymerase (PARP) inhibitors (PARPi) have been approved both for initial treatment of EOC and as its maintenance treatment. PARPi have also been found to act regardless of BRCA status or homologous recombination (HR) deficiency. Several trials testing PARPi early in maintenance therapy are in progress and their results will shed light on the optimal timing of maintenance therapy that gives the most benefit with least toxicity. Right patient selection for maintenance treatment is also a challenge. Hence, though PARPi are emerging as a promising maintenance treatment in recurrent EOC with prolongation of progression free survival (PFS), results from further trials and overall survival (OS) data from current trials are awaited to fulfill the gaps in understanding the role of this pathway in treatment of EOC. This review discusses the current therapies for EOC, challenges in the treatment of recurrent EOC, recent developments and trials in recurrent EOC maintenance with special focus on PARPi and future perspectives.

Pressurized intraperitoneal aerosol chemotherapy procedure for nonresectable peritoneal carcinomatosis: First Indian study.

BACKGROUND: Peritoneal carcinomatosis (PC) is a common evolution of abdominal cancers and is associated with poor prognosis. A few selected patients have option of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, but majority who are not eligible for curative approach can undergo pressurized intraperitoneal aerosol chemotherapy (PIPAC). It is an emerging field of research with major therapeutic potential. It is a safe and innovative approach, which enhances the effect of chemotherapy without major toxicity. METHODS: Between June 2017 and December 2017, 21 PIPAC applications in seven patients with standard chemotherapy regimen every 6 weeks at 37°C and 12 mmHg for 30 min was performed. The patients' demographics, perioperative findings, adverse events, and outcomes were prospectively recorded. RESULTS: Twenty-one PIPAC administrations were performed in 7 patients with PC from various pathologies. The median hospital stay was 1 day. All the patients had symptomatic relief with complete resolution of ascites. There was no major perioperative complications. CTCAE Grades 1 and 2 were observed in three patients, for abdominal pain and nausea. Renal and hepatic functions were not impaired. Of the seven patients, one patient had complete histological remission; three patients had partial response, one had stable disease and one patient had no response with clinical progression. CONCLUSION: Our results show the feasibility and safety of PIPAC in Indian patients. The procedure has low morbidity with no mortality with the short learning curve. It can be easily adapted for Indian patients with diffuse PC as a palliative option apart from systemic chemotherapy.

Pressurized IntraPeritoneal Aerosol Chemotherapy vs. intravenous chemotherapy for unresectable peritoneal metastases secondary to platinum resistant ovarian cancer - study protocol for a randomized control trial.

BACKGROUND: Despite optimal surgery and appropriate first-line chemotherapy, ∼70-80 % of patients with epithelial ovarian cancer will develop disease relapse. The prognosis is poor especially for women with Platinum resistant ovarian cancer. The standard treatment for these groups of patients is non-platinum-containing chemotherapy like taxanes, anthracyclines, gemcitabine, topotecan, and trabectedin. These drugs in various combinations and sequences provide modest survival or symptomatic benefit but with significant side effects. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a minimally-invasive drug-delivery technique specifically addressing limited tissue penetration and poor drug distribution with promising results. PIPAC is a novel method of delivering normothermic chemotherapy into the abdominal cavity as an aerosol under pressure. This concept seems to enhance the effectiveness of intra peritoneal chemotherapy by taking advantage of the physical properties of gas and pressure by generating an artificial pressure gradient and enhancing tissue uptake and distributing drugs homogeneously within the closed and expanded peritoneal cavity. Thus, due to the high local bioavailability during PIPAC, the chemotherapy dosage can be reduced which in turn largely prevents systemic side effects and organ toxicity. METHODS: The study aims to investigate the therapeutic efficacy measured as objective tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, of PIPAC in comparison with conventional Intravenous chemotherapy for women with recurrent platinum resistant ovarian cancer with peritoneal metastasis (PM). Consecutive patients diagnosed with PM secondary to platinum-resistant ovarian cancer will be randomized to PIPAC group or IV chemotherapy group. The primary objective of this study is to determine the efficacy after three cycles of PIPAC with cisplatin and doxorubicin in comparison with six cycles of systemic chemotherapy. The secondary outcome measures include morbidity and mortality, overall survival and disease specific survival. Analysis is by intention to treat. AIM: Assess the objective tumour response of PIPAC in comparison with systemic intravenous chemotherapy for women with platinum-resistant ovarian cancer. STUDY TYPE: Prospective randomized control intervention trial. INTERVENTION MODEL: IV Chemotherapy group (Control group) PIPAC group (Experimental group). MASKING: Open label. PRIMARY PURPOSE: Treatment. SAMPLE SIZE: Calculated sample size is 97 and rounded to 100. For each treatment group sample size of 50 will be considered. PRIMARY OUTCOME CRITERIA: Objective tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.Secondary outcome criteria: Morbidity;Disease-specific survival (months between inclusion and death due to ovarian cancer);OS (months between inclusion and death due to any cause);CA 125 levels. DISCUSSION: PIPAC in women with platinum resistant ovarian PM has good response owing to superior tissue penetration and better drug distribution. The procedure is safe and well tolerated owing it to its minimal invasiveness. Typical side-effects of systemic chemotherapy, such as alopecia, peripheral neurotoxicity, nausea and myelosuppression are absent. We expect reduction of ascites with symptomatic relief and CA 125 levels. PIPAC is a novel technique for selected patients with platinum resistant ovarian PM and further investigation in comparative clinical trials with conventional chemotherapy will establish its role as a good palliative treatment option. ETHICS COMMITTEE APPROVAL: Obtained. STATUS: Recruiting. TRIAL REGISTRATION NUMBER: REF/2018/08/021223 Registered on Clinical Trials Registry - India (CTRI); www.ctri.nic.in.

Impact of extent of parietal peritonectomy on oncological outcome after cytoreductive surgery and HIPEC.

BACKGROUND: In peritoneal surface malignancy (PSM), in spite of optimal cytoreductive surgery (CRS), majority of recurrences that occur are intraperitoneal. In patients with PSM, studies employing fluorescent imaging and microscopic examination have shown normal looking peritoneum may harbor active disease. This study was done to assess the recurrence pattern, oncological outcomes, and morbidity and mortality of the extent of peritonectomy in patients who underwent total parietal peritonectomy (TPP) or involved field peritonectomy (IFP) as a part of the procedure during CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This was a retrospective analysis of prospectively collected data, from February 2013 to December 2017. A total of 163 patients with PSM underwent TPP or IFP with CRS plus HIPEC. Their oncological outcomes, recurrence pattern, postoperative morbidity and mortality were analyzed. RESULTS: Of the 163 cases, the primary organs of origin were ovary, colorectal, appendicular pseudomyxoma, stomach, mesothelioma and others (67.4%, 16.5%, 6.1%, 4.9%, 2% and 2%), respectively. TPP was performed in 70 patients and IFP in 93 patients. TPP group had higher mean PCI (16 vs. 14), longer duration of surgery (11 vs. 9 h), and more blood loss (1,243 vs. 675 mL). Overall G3-G4 morbidity was comparable in both groups (42.8% vs. 33.3%) as was mortality (5.7% vs. 4.4%). Kaplan-Meier analysis showed that with a median follow-up of 45 months, TPP group had a recurrence-free survival (RFS) of 26 months and overall survival (OS) was yet to be achieved, whereas the IFP group had a RFS and OS of 21 and 43 months, respectively. CONCLUSIONS: Performing TPP reduces the chance of missing the microscopic disease, therefore can minimize local recurrence, and better oncological outcomes. TPP can be performed with acceptable morbidity and mortality, at the cost of increased duration of surgery and higher blood loss.

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)杛ibose 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

Evolving trends in lung cancer: Epidemiology, diagnosis, and management

Lung cancer is one of the deadliest cancers globally and accounts for most of the cancer?related deaths in India. Comprehensive data on lung cancer in India are lacking. This review aimed to discuss the epidemiological trends of lung cancers and driver mutations as well as the recent advancements in molecular diagnostics and therapeutic options primarily in non杝mall cell lung cancer (NSCLC) in India. Electronic databases, such as PubMed and Google Scholar, were searched to retrieve the relevant literature published in the past 5 years. As per the GLOBOCAN 2018 report, lung cancer was ranked the fourth leading cause of cancer (5.9% cases) in India, in all ages and sexes. Furthermore, 63,475 of all cancer?related deaths (8.1%) were attributed to lung cancer (cumulative risk 0.60), making it the third leading cause of cancer?related mortality. The common targets for treatment in lung cancer patients mainly include EGFR mutation, ALK and ROS1 rearrangements and PDL1 expression. In India, EGFR mutations and ALK re?arrangement are commonly reported, but there is limited data of PD?L1 expression. Molecular testing has gained importance as several biomarkers are being targeted to treat lung cancer patients. Surgery, radiotherapy, systemic chemotherapy, and personalized molecular?targeted therapy prolong the overall survival (OS) in patients with NSCLC. Although chemotherapy and molecular?targeted therapies have greatly improved the clinical outcomes, prolonged disease control could not be attained in NSCLC patients without a driver mutation. In this situation, immunotherapy seems to be potentially beneficial to obtain long?lasting disease control with minimal adverse events.