Shaesta Mehta

D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

BackgroundPatients with locally advanced resectable gastric cancers are increasingly offered neoadjuvant chemotherapy (NACT) following the MAGIC and REAL-2 trials. However, information on the toxicity of NACT, its effects on perioperative surgical outcomes and tumor response is not widely reported in literature.MethodsAnalysis of a prospective database of gastric cancer patients undergoing radical D2 gastrectomy over 2 years was performed. Chemotherapy-related toxicity, perioperative outcomes and histopathological responses to NACT were analyzed. The data is presented and compared to a cohort of patients undergoing upfront surgery in the same time period.ResultsIn this study, 139 patients (42 female and 97 male patients, median age 53 years) with gastric adenocarcinoma received NACT. Chemotherapy-related toxicity was noted in 32% of patients. Of the 139 patients, 129 underwent gastrectomy with D2 lymphadenectomy, with 12% morbidity and no mortality. Major pathological response of primary tumor was noted in 22 patients (17%). Of these 22 patients, lymph node metastases were noted in 12 patients. The median blood loss and lymph node yield was not significantly different to the 62 patients who underwent upfront surgery. Patients who underwent upfront surgery were older (58 vs. 52 years, P <0.02), had a higher number of distal cancers (63% vs. 82%, P <0.015) and a longer hospital stay (11 vs. 9 days, P <0.001).ConclusionsPerioperative outcomes of gastrectomy with D2 lymphadenectomy for locally advanced, resectable gastric cancer were not influenced by NACT. The number of lymph nodes harvested was unaltered by NACT but, more pertinently, metastases to lymph nodes were noted even in patients with a major pathological response of the primary tumor. D2 lymphadenectomy should be performed in all patients irrespective of the degree of response to NACT.

Infusion chemotherapy with cisplatinum and fluorouracil in the treatment of locally-advanced and metastatic gallbladder cancer

BACKGROUND Gallbladder cancer (GBC) has a poor prognosis. Chemotherapy is traditionally considered to be ineffective. The goal of the current study was to evaluate the efficacy of infusional 5-fluorouracil (5-FU) and cisplatinum (CDDP) in patients with inoperable GBC. MATERIALS AND METHODS A total of 65 patients with inoperable GBC received palliative chemotherapy with CDDP and 5-FU. All the patients had clinically measurable disease as well as adequate bone marrow, hepatic, and renal function. Response was assessed after three cycles of chemotherapy. RESULTS A total of 19 patients had locally advanced unresectable cancer and 46 patients had metastatic cancer. There were 39 females and 26 males, with a median age of 50 years. A total of 212 chemotherapy cycles were administered to the patients. Response evaluation after three cycles of chemotherapy revealed complete response in five patients [7.69%; 95% confidence interval (95% CI): 2.87-16.22], partial response in 17 patients (26.15%; 95% CI: 16.57-37.81), stabilization of disease in 9 patients (13.85%; 95% CI: 6.96-23.88), and progression in 21 patients (32.30%; 95% CI: 21.80-44.35). At 6 months 44.6% patients were alive and 18.5% patients were alive at 12 months. The median overall survival was 5.7 months and the median time to disease progression was 3.1 months. This chemotherapy combination was well tolerated. There were no chemotherapy-related deaths. CONCLUSIONS Infusion chemotherapy with CDDP and 5-FU appears to have a fair amount of activity in patients of inoperable GBC, with acceptable toxicity. Tumor shrinkage following treatment with this regimen enabled surgical resection in two patients. We believe that this promising combination must be tested against gemcitabine-based combinations in patients with inoperable GBC.

Simultaneous gallbladder and bile duct cancers: revisiting the pathological possibilities

The pathogenesis of gallbladder cancer presenting synchronously with malignancy of the bile duct has not been clearly understood. The possible causes for the simultaneous presence of these tumors could be due to local spread, metastases, de novo multifocal origin, or as part of a field change in the extrahepatic biliary apparatus. In this article, we discuss the cases of four patients with simultaneous gallbladder and bile duct malignancies and analyze their individual pathologies to provide an explanation into the mechanisms that may play a role in such conditions.

Is there a role for estrogen and progesterone receptors in gall bladder cancer

BACKGROUND/AIMS The concept of metaplastic and non-metaplastic types of gall bladder cancer and the likelihood of hormone receptor expression in the nuclei of tumour cells raised the possibility of a potential role for anti-estrogen therapy in gall bladder cancer. This study was carried out to determine the hormone receptors (ER/PR) expression level in gall bladder cancer using specific immunohistochemical assays and correlate it with patient and tumour histopathological characteristics. PATIENTS AND METHODS Histopathological tumour specimens of 62 patients who underwent a radical cholecystectomy were analysed. Pronase pretreatment and primary monoclonal antibodies were used to perform immunohistochemical analysis for ER and PR. RESULTS The histology was adenocarcinoma--predominantly, moderately to poorly differentiated (91%). Gallstones were present in 90% of the individuals. Of the 62 specimens analysed, 62 (100%) and 61 (98%) were negative for ER and PR, respectively. CONCLUSION The high incidence of gallstone-related gall bladder cancer in India is associated with metaplasia and a tendency to poorer differentiation in the tumour histology. These tumours are consequently less likely to express hormone receptors. Thus, there does not seem to be a role for anti-hormone therapy in patients with histogenesis similar to that seen in India.

Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancers: results from phase II randomized study.

PurposeThis trial was undertaken to compare the rates of resectability between patients treated with neoadjuvant concurrent chemoradiation vs. boosted radiotherapy alone.Materials and methodsPatients with clinically unresectable rectal cancer were randomized to receive external beam radiation therapy (EBRT) to pelvis (45 Gy) with concurrent oral Capecitabine (CRT group; Arm 1) or EBRT to pelvis (45 Gy) alone followed by 20 Gy dose of localized radiotherapy boost to the primary tumor site (RT with boost group, Arm 2). All patients were assessed for resectability after 6 weeks by clinical examination and by CT scan and those deemed resectable underwent surgery.ResultsA total of 90 patients were randomized, 46 to Arm 1 and 44 to Arm 2. Eighty seven patients (44 in Arm 1 and 41 in Arm 2) completed the prescribed treatment protocol. Overall resectability rate was low in both the groups; R0 resection was achieved in 20 (43 %) patients in Arm 1 vs. 15 (34 %) in Arm 2. Adverse factors that significantly affected the resectability rate in both the groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological response was seen in 7 and 11 %, respectively. There was greater morbidity such as wound infection and delayed wound healing in Arm 2 (16 vs. 40 %; p = 0.03).ConclusionEscalated radiation dose without chemotherapy does not achieve higher complete (R0) tumor resectability in locally advanced inoperable rectal cancers, compared to concurrent chemoradiation.

Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.].

Factors influencing response to neoadjuvant chemoradiation and outcomes in rectal cancer patients: tertiary Indian cancer hospital experience

BACKGROUND In the treatment of rectal cancers several randomized trials have demonstrated benefits of neoadjuvant chemoradiotherapy (NACRT) in downstaging as well as survival among these patients. We investigated the patient and tumor related variables dictating the outcomes in these patients. METHODS Biopsy proven treatment naive 182 rectal cancer patients underwent NACRT from June 2006 to December 2010. The entire patients received long course conventionally fractionated external beam radiotherapy with concurrent oral Capecitabine. At 6 weeks from completion of NACRT clinico-radiological assessment was carried out for surgical feasibility. All patients were given postoperative adjuvant chemotherapy either single agent or multi drug regimen depending upon biopsy report. RESULTS Among 182 patients, 131 (72%) underwent surgery and initial T stage and signet ring cell morphology were major determinant of operability. Among the 131 operated patients at median follow up of 36 months, 94 (72%) are alive and disease free. With a median follow up of 42 months the 5-year disease free survival (DFS) and overall survival (OS) was 60% and 77%. The majority of the failures were distal but with more advanced disease at presentation both local and distal failures were similar. While assessing survival by multivariate analysis patients having positive nodes post-surgery had a significantly poorer DFS (P=0.001), while signet ring cell morphology and pre-treatment carcino-embryonic antigen (CEA) levels strongly influenced OS (P=0.03). CONCLUSIONS The outcome of our patients were similar to World Literature and signet ring cell morphology, pre-treatment CEA level, and pathological nodal staging all were influential in determining survival. Besides this, the study also highlights the fact that tumours with signet ring cell morphology appearing in younger population with poor survival needs prospective evaluation for more intense CRT regimen and aggressive surgical resections.

Combined brachytherapy and external beam radiation: an effective approach for palliation in esophageal cancer

Purpose Palliation of dysphagia is a challenge in advanced esophageal cancer. The addition of external beam radiotherapy (EBRT) to intraluminal brachytherapy (ILBT) has shown significant improvement in dysphagia relief and symptom scores. The aim of the present study was to evaluate the efficacy of combined use of ILBT and EBRT. Material and methods The medical records of 148 patients with advanced/metastatic esophageal cancer were screened from January 2008 to April 2014, and 74 patients were found eligible for the analysis. All patients received two fractions of 8 Gy each of ILBT, followed by EBRT. Patients were assessed for the symptom scores of dysphagia, odynophagia, regurgitation, and chest pain and weight was recorded periodically. Results For a median follow-up of 6 months, the median OS was 9.5 months (95% CI: 7.5-10.5). The median dysphagia free survival was 6 months (95% CI: 4.8-7.1). The scores for dysphagia significantly improved after completion of 1st ILBT (p = 0.000), 2nd ILBT (p = 0.000), and at 3 months after EBRT compared to ILBT (p = 0.02). Overall 47% had improvement in dysphagia scores and 35% maintained the improvement of scores till last follow up. There was significant improvement in weight after completion of ILBT (p = 0.001) and at 3 months after completion of EBRT (p = 0.00). Twenty nine (39%) patients required nasogastric (NGT) insertions and 12 (16%) needed hospitalization for supportive care. 36.4% had complications in the form of stricture (27%), fistula (5.4%), and bleeding (4%). Conclusions Palliative radiotherapy is an effective alternative for palliation of dysphagia with improvement in symptom scores being evident and sustained. The results of this clinical audit were comparable with those from the trial setting.

Intensity modulated radiation therapy (IMRT) is not superior to three-dimensional conformal radiation (3DCRT) for adjuvant gastric radiation: A matched pair analysis

AIMS To compare three-dimensional conformal radiation (3DCRT) and Intensity Modulated Radiation Therapy (IG-IMRT) for adjuvant gastric irradiation. SUBJECTS AND METHODS From Jan 2010-Aug 2013, all patients undergoing 3DCRT and IG-IMRT were included. Systemic chemotherapy included 1 cycle before and 2 cycles after chemoradiation. Planning Target Volume (PTV) received 45 Gy/25 fractions/5 weeks with concurrent capcetabine 825 mg/m2 bid. Matched pair analysis was performed to evaluate imbalance in two cohorts if any. Common Toxicity Criteria for Adverse Event (CTCAE) vs 3.0 was used to record gastrointestinal (GI), hematological (HL), and renal toxicity during treatment and follow-up. Patterns of recurrence were documented. Mann-Whitney U test was used for statistical comparison. RESULTS Of the 51 patients, 26 received 3DCRT and 25 IMRT. IMRT led to decrease in dose received by right and left kidney (12.4 Gy and 7.1 Gy and 29 Gy vs 8.2 Gy; P<0.001). Overall, 17.6% and 19.6% patients had grade II GI and HL toxicity and 3.9% and 5.9% had grade III GI and HL toxicity. No difference was observed in acute grade II-V GI or HL toxicity (11.5% vs 24%, P=0.07; 7.6% vs 20% P=0.20) or late GI, HL, or renal toxicity between 3DCRT and IMRT. No difference was observed in patterns of local relapse (11.5% vs 12%, P=0.14) or overall survival (39% and 38% (P=0.97)) between 3DCRT and IMRT. CONCLUSIONS 3DCRT and IMRT are equivalent in terms of toxicity and local control.

Cost-Effectiveness of Aspirin Adjuvant Therapy in Early Stage Colorectal Cancer in Older Patients

Background & Aims Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older. Methods Two five-state Markov models were constructed separately for Stage I and II colorectal cancer using TreeAge Pro 2014. Two hypothetical cohorts of 10,000 individuals at a starting age of 65 years and with colorectal cancer in remission were put through the models separately. Cost-effectiveness of aspirin was evaluated against no treatment (Stage I and II) and capecitabine (Stage II) over a 20-year period from the United States societal perspective. Extensive one-way sensitivity analyses and multivariable Probabilistic Sensitivity Analyses (PSA) were performed. Results In the base case analyses, aspirin was cheaper and more effective compared to other comparators in both stages. Sensitivity analyses showed that no treatment and capecitabine (Stage II only) can be cost-effective alternatives if the utility of taking aspirin is below 0.909, aspirin’s annual fatal adverse event probability exceeds 0.57%, aspirin’s relative risk of disease progression is 0.997 or more, or when capecitabine’s relative risk of disease progression is less than 0.228. Probabilistic Sensitivity Analyses (PSA) further showed that aspirin could be cost-effective 50% to 80% of the time when the willingness-to-pay threshold was varied from USD20,000 to USD100,000. Conclusion Even with a modest treatment benefit, aspirin is likely to be cost-effective in Stage I and II colorectal cancer, thus suggesting a potential unique role in secondary prevention in this group of patients.