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.

Bowel Anastomosis After or Before HIPEC: A Comparative Study in Patients Undergoing CRS+HIPEC for Peritoneal Surface Malignancy.

BACKGROUND: Anastomotic leak after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. There is no consensus statement regarding the optimal timing for bowel anastomoses to perform after or before HIPEC. METHODS: Patients who underwent CRS+HIPEC and had at least one bowel anastomosis were retrospectively analyzed to evaluate if timing of anastomosis done after or before HIPEC had an impact on bowel complication rates (anastomotic leak and perforation). RESULTS: From 2013 to 2019, 214 of 370 patients underwent CRS+HIPEC and had at least one bowel anastomosis. Of these 214 patients, 104 and 110 patients had anastomosis after and before HIPEC, respectively. A total of 324 anastomoses were performed, with a mean of 0.87 anastomoses per patient (range 1-4). The incidence of anastomotic leaks was comparable between the pre- and post-HIPEC groups (3.6% vs. 4.8%; p > 0.05), as was the bowel complication rate (7.6% vs. 7.2%). After multivariate analysis, prior surgical score >1 (odds ratio [OR] 4.3), recurrent cancers (OR 7.4), and more than two anastomosis (OR 3.8) were considered independent risk factors for bowel complications. CONCLUSION: Anastomosis of the bowel performed after or before HIPEC does not affect bowel complication rates (leak/perforation). Higher prior surgical score, surgery for recurrent cancers, and more than two bowel anastomosis are independent risk factors for predicting bowel complications. Prehabilitation, standardization of steps, immediate attention and repair of serosal tears, and thorough inspection of the bowel before closure helps to decrease bowel complications. The timing of anastomosis can be at the discretion of the surgeon.

Can Low-cost Indo Cyanine Green Florescence Technique for Sentinel Lymph Node Biopsy Replace Dual Dye (Radio-colloid and Blue Dye) Technique in Early Breast Cancer: A Prospective Two-arm Comparative Study.

BACKGROUND: The objective of this study was to assess the detection and accuracy of sentinel lymph node (SLN) biopsy (SLNB) using the low-cost indocyanine green (ICG) fluorescence method and to compare this method with the gold standard dual-dye method (radio-colloid + methylene blue dye [MB]). MATERIALS AND METHODS: One hundred patients with node-negative early breast cancer assessed clinically and by ultrasound axilla underwent an SLNB procedure using technetium-99m radio-colloid, MB, and ICG. The detection rate of SLNs and positive SLNs and the number of SLNs were compared. The injection safety of ICG and MB was evaluated. RESULTS: One hundred female patients with a median age of 52.3 years participated in the study. Sixty-eight percent had a body mass index < 25, 85% presented with a palpable lump, of which 59% were in the outer quadrant. SLNs were identified in all 100 cases. A total of 290 SLNs were removed (mean, 2.9; range, 1-6). The identification rate with dual dye was 94%, whereas with ICG alone, it was 96%. The SLNB sensitivity rate and false negative rate were 97.6% versus 93.2% and 3.1% versus 6.2% in the ICG and dual-dye combination, respectively. None of the patients had any local or systemic reaction with ICG; 3 patients with blue dye had tattooing and staining of skin. CONCLUSION: ICG fluorescence imaging permits real time visualization of lymphatics and provides an additional dimension to SLN biopsy that is safe and effective. These results confirm high sensitivity for fluorescence localization with comparable performance to the gold standard. ICG can reliably replace dual dye and be employed as a sole tracer for SLNB in early breast cancer.

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.

Assessment of Tumor Response and Resection Rates in Unresectable Colorectal Liver Metastases Following Neoadjuvant Chemotherapy with Cetuximab.

To investigate efficacy and safety of cetuximab combined with neo adjuvant chemotherapy regimen in patients with unresectable colorectal liver. This was a prospective trial with rate of Ro liver metastases resection as primary end point. Between January 2010 and December 2014, 46 patients with unresectable liver metastases from colon or rectum were enrolled. Patients received Cetuximab along with neoadjuvant chemotherapy where 34 (74 %) and 12 (2 6 %) patients received FOLFOX and FOLFIRI, respectively. They were assessed for response after 2-3 cycles by CT scan. Patients with resectable disease were offered liver surgery within 3-6 weeks of the last treatment cycle. The primary end point was resection rate of liver metastases, which was evaluated in all patients. Secondary end points were response rate according to Response evaluation criteria in solid tumors (RECIST) criteria, perioperative morbidity and mortality. An objective response was observed in 28 (60.9 %) patients. Seven (15.2 %) patients were reported radiologically to have a complete response (CR); 21 (45.7 %) patients had radiological partial response (PR). An additional 12 patients (26.1 %) demonstrated stable disease (SD) and only six patients (13.0 %) had disease progression (PD). Microscopically complete resections (R0 resection) was performed in all 28 patients (60.9 %). The most frequent toxicities were skin rash and diarrhoea. There was no operative mortality. Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. Complete resection of previously unresectable colorectal liver metastases can be performed with minimal morbidity and mortality. This therapeutic strategy involves a multimodal approach.

Intraoperative Frozen Section Evaluation of Sentinel Lymph Nodes in Breast Carcinoma: Single-Institution Indian Experience.

Sentinel lymph node biopsy is an established way of predicting axillary nodal metastasis in early breast cancer. Intraoperative frozen sections (FS) of sentinel lymph nodes (SLNs) can be used to detect metastatic disease, allowing immediate axillary lymph node dissection. The purpose of this study was to evaluate the accuracy of intraoperative frozen sections in evaluation of sentinel lymph nodes in cases of breast cancer. Between March 2006 and August 2010, a total of 164 patients with clinically node-negative operable breast cancer were subjected to sentinel lymph node biopsy of axillary lymph nodes using preoperative peritumoral injection of radioactive colloid and methylene blue. Intraoperative identification of sentinel nodes was done using a handheld gamma probe and identification of blue-stained nodes. The nodes were sent for frozen section examination. The results of frozen section were compared with the final histopathology. Out of the 164 cases, metastases were detected in SLN by frozen section in 38 cases. There were three false-negative cases (all showing micrometastasis on final histopathology). FS had sensitivity of 92.6 %, specificity of 100 %, and overall accuracy of 98.1 %. The positive predictive value was 100 %, and the negative predictive value was 97.6 %. FS for diagnosis of metastasis of SLNs is reliable. Patients with negative SLNs by the FS diagnosis can avoid reoperation for axillary lymph node dissection. However, FS may fail to detect micrometastases, especially in cases with small tumors.

Prospective randomized study comparing robotic-assisted hysterectomy and regional lymphadenectomy with traditional laparotomy for staging of endometrial carcinoma -initial Indian experience.

Robotic assisted hysterectomy with regional lymphadenectomy is increasingly used for the treatment of endometrial carcinoma. In the present study we evaluated the feasibility and technique of robotic assisted hysterectomy and lymphadenectomy in patients with endometrial carcinoma. A prospective randomized study was undertaken from July 2011 to June 2012, in 50 consecutive patients with carcinoma endometrium. Demographic (age, BMI) and perioperative data (operating time, estimated blood loss, total number of lymph nodes retrieved, hospital stay, conversion to open procedure, intraoperative and postoperative complications) of robotic assisted surgery were compared with open staging procedure. Mean age of the patient and BMI in both groups were comparable with no significant difference. Estimated blood loss (81.28 ml), hospital stay (1.94 days) and perioperative complications were significantly less in robotic assisted group in comparison to open method. Mean number of lymph nodes removed were 30.56 versus 27.6 which is suggestive of significant difference statistically. Operative time decreased as the experience of the surgeon increased but still significantly remained higher than the open procedure after 25 robotic assisted surgeries. All robotic surgeries were completed successfully without converting to open method. Robotic assisted staging procedure for endometrial carcinoma is feasible without converting to open method, with the advantages of decreased blood loss, short duration of hospital stay and less postoperative minor complications. Operative time will decrease further as the experience of surgeon increases. Para-aortic lymph node dissection is easily done and with a better ergonomics for surgeon.

Intraperitoneal chemotherapy for epithelial ovarian cancer - single center experience.

Majority of intraperitoneal (IP) chemotherapy complications were related to the chemoport. Aim of our study was to find the means of reducing complications of IP chemoport, to increase the benefits of IP chemotherapy. During January 2007 to December 2010, hundred consecutive patients of stage III epithelial ovarian cancer who had optimal cytoreduction underwent chemoport insertion during laparotomy. Initial 20 cases had 14.3F Bard IP chemoport, and later cases had 9.6Fr single lumen venous port inserted intraperitoneally. Entry point into the peritoneum was single, 6 cm lateral to the umbilicus and double purse-string suture taken around the catheter to prevent peri-catheter backflow of ascitic fluid or drug. Modified IP chemotherapy regimen (SWOG-9912 trial) was used. Age of the patient ranged from 34 years to 76 years. In total 600 cycles, 516 cycles (86 %) were completed. Seventy patients (70 %) received all the 6 cycles by IP route. Two in the initial 10 patients had vaginal leak, for whom first 2 cycles were given by IV route and then shifted to IP route. Subsequently all cases had double layer closure of vaginal vault. Nine patients (9 %) had port related complications, in which 8 were transient. Catheter block was seen in 5 cases, of which 4 salvaged by heparin injection lock for 2 h and in subsequent cases IV port access catheter with valve replaced the fenestrated IP catheter. None of the IV catheters had the block. Four cases had backflow of fluid around catheter collecting around the port chamber site. Two patients had severe abdominal pain due to dense adhesions and further cycles were completed by IV route. Cisplatin was replaced with carboplatin in 5 cases with severe toxicity. Longest follow-up is 4 years with median follow up of 1.8 years.70 % are disease free on follow up. Local recurrence rate was 18 and systemic in 8 cases. Mortality rate is 4 %. Complications of IP ports are low when insertion is done meticulously with a dedicated team. With modified IP dose and drug regimen, side effects are less and most patients can complete all the desired cycles.

Value of frozen section and primary tumor factors in determining sentinel lymph node spread in early breast carcinoma.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is the standard of care to assess the metastasis in breast carcinoma. Accuracy of intraoperative frozen section examination to evaluate SLN in detecting metastasis is important as it determines the further management of axilla. Primary tumor characteristics determining the metastasis to the lymph node will help in predicting the probability of spread and to determine the nature of disease. It also helps in refining selection of patients for SLNB. We evaluated all these criteria on Indian patients for the better management. MATERIALS AND METHODS: Between January 2005 and April 2009, 114 consecutive patients of all age group of both sex, with cytology or biopsy proven carcinoma breast, clinical stage T1/T2 N0 M0 at Manipal Comprehensive Cancer Center, Manipal Hospital, Bangalore were subjected to SLNB and introperative frozen examination. First 75 cases had complete axillary clearance irrespective of SLNB result and subsequently, positive cases underwent axillary lymph node dissection (ALND). Age of the patient and primary tumor characteristics like size, grade, lymphovascular invasion (LVI), perineural invasion, ER/PR status, Her2-neu status and histological sub-types were evaluated for predicting the SLN metastasis. Feasibility of SLNB in previously treated patient is also evaluated. RESULTS: The age of the patient ranged from 23 to 87 years and its association with SLN spread is not significant. Frozen section examination had accuracy of 97.37% in determining metastatic sentinel node with sensitivity of 96.15% and specificity of 100% with value P < 0.001. SLN remained significant indicator of the status of rest of axilla with value P < 0.001. Primary tumor characteristics like histological subtypes, grade (P = 0.353), ER/PR status (P = 0.839), Her2-neu status (P =0.296) were not significantly associated with SLN metastasis. Size of the primary tumor (P = 0.002), LVI (P < 0.001), perineural invasion (P = 0.084+) were significant factors determining the SLN metastasis. SLNB evaluation had no false negative values in previously treated breast. CONCLUSION: SLNB is a valuable method of determining the axillary nodal metastasis. Intraoperative frozen section examination is highly ac-curate in detecting nodal metastasis. Primary tumor characteristics like size, LVI and perineural invasion are significant in predicting SLN metastasis. SLNB remains an important method of predicting axillary metastasis even in previously treated breast carcinomas.

Sentinel lymphnode biopsy in early breast cancer using methylene blue dye and radioactive sulphur colloid - a single institution Indian experience.

BACKGROUND: Axillary lymph node dissection is an established procedure in breast cancer staging. However, it is associated with unpleasant side effects. A promising alternative to assess axillary lymph node status in early breast cancer patients is Sentinel Lymph Node Biopsy (SLNB). Isosulfan blue has traditionally been the dye used to identify the Sentinel Lymph Node (SLN). This article is a validation study of SLNB using methylene blue dye and radioactive sulphur colloid in early breast cancer Indian patients. MATERIALS #ENTITYSTARTX00026; METHODS: With written informed consent, 100 patients with cytology or biospy proven carcinoma breast, clinical stage T1/ T2 N0 M0, underwent SLNB using combination of methylene blue dye & radioactive technetium 99m sulphur colloid as a part of validation study from June 2003 to February 2006. After validation study, from March 2006 to February 2007, 35 patients have undergone SLNB followed by complete axillary clearance in only those patients with SLNB being positive for metastases. RESULTS: In all 100 patients of the validation study SLN was identified. Total number of cases with positive axillary nodes was 27, out of which SLN was only positive node for metastases in 69% of cases. The overall sensitivity, specificity, positive predictive valve and negative predictive valve of SLNB 96.2%, 100%, 100% and 98.6% respectively with false negative rate of 3.7%. In subsequent 35 patients who underwent SLNB followed by complete axillary clearance, SLNs was identified in all the cases. CONCLUSIONS: SLNB is effective in early breast cancer patients of Indian population. SLNB using combination of methylene blue dye and radio-active Tc99m sulphur colloid can stage the axilla with high accuracy & low risk of false negativity in early breast cancer patients.