Prognostic Factors for Recurrence in Esophageal Cancer Patients Treated With Neoadjuvant Therapy and Surgery: A Single-institution Analysis.

Background The purpose of this study is to analyze potential predisposing factors for a higher risk of recurrence in our esophageal cancer patients managed with neoadjuvant chemotherapy, radiation therapy, and surgery, and to determine their impact on disease-free survival (DFS) and time to recurrence. Methods A total of 154 of 232 patients staged T1b to T4a managed electively at our institute from July 2005 through July 2015 with a tri-modality approach were retrospectively evaluated. Basic demographic, clinical, radiological, operative, and pathological disease-related parameters, along with waiting time for surgery and type of neoadjuvant modality used, were assessed as potential risk factors. The primary endpoint was the impact of these on the risk of recurrence. The secondary endpoint was to study their relation on DFS and time to recurrence. Results The recurrence rate in this particular study was 33.1% over a median follow-up of 35 months (interquartile range = 19-50.3). The median time to recurrence was 12 months, and 94% of recurrences occurred within two years. The median DFS was 33 months, and the one- and three-year DFS was 90% and 72%, respectively. On univariate and multivariate analysis, a complete pathological response (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.41-10.11), negative resection margins (HR: 5.9, 95% CI: 1.69-20.45), and a low nodal index (HR: 6.3, 95% CI: 1.37-28.67 for an index of 0.1-0.2; and HR: 15.2, 95% CI: 0.96-241.73 for an index of >0.2) were found as statistically significant (P = < 0.05) for risk to recurrence. In addition to these three, a low comorbidity index (P = 0.03; HR: 3.5; 95% CI: 1.16-10.52) was an individual positive predictor of DFS. Conclusions A complete pathological response, low nodal index, and margin-negative resection were the identified predictors of freedom from recurrence, with a better DFS and a low comorbidity index as additional indicators of prolonged DFS.

Radiotherapy Outcome for Pediatric Pelvic Ewing Sarcoma.

OBJECTIVE: To evaluate the outcomes of patients undergoing radiotherapy for primary local control of pelvic ewing sarcoma (ES). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Shaukat Khanum Memorial Cancer Hospital, Lahore, from January 2010 to October 2015. METHODOLOGY: Patients with primary pelvic ES were included in the analysis and all other primary disease sites were excluded. All of them were treated with radiotherapy and followed the EuroEwing-99 chemotherapy protocol. Tumor volume, relapse and metastases were noted. RESULTS: There were 13 patients with pelvic ES. The median age at the time of diagnosis was 15 years with IQR of 7 years (range 2-19 years). Tumor volume was more than 400ml in more than 50% of the patients. Eight patients (61.5%) had local relapses and 5 patients (38.5%) had combined local and distant disease metastases. CONCLUSION: These results showed poor local control and overall survival in local pelvic ES cases in children and adolescents. Intensity modulated radiotherapy (IMRT) can be used to deliver higher doses of radiation. Compressed cycles of chemotherapy should be evaluated in local setting.

Efficacy And Toxicity Of Carboplatin/Paclitaxel Based Chemoradiation For Localized Oesophageal Cancer.

BACKGROUND: The management of Oesophageal and Gastroesophageal junction cancers is challenging. Multimodality therapy with carboplatin/paclitaxel based chemoradiation (CRT) and surgery shows improved efficacy. In this study, we wanted to establish the efficacy and safety of CRT for neoadjuvant and radical treatment of localized oesophageal cancer. METHODS: Patients with oesophageal cancer, registered between September 2013 and October 2014 were reviewed retrospectively. Toxicity and efficacy analysis in the form of radiological response rate, R0 resection rate, Progression free survival (PFS) and overall survival (OS) was performed on 102 patients who received radical carbo/pacli induction chemotherapy followed by CRT. Impact of Surgery was seen on PFS and OS. RESULTS: Males and females were 71 (51.1%) and 68 (48.9%) respectively, with squamous cell carcinoma being the predominant histology (92%). Majority of patient belonged to T3/4 and N1 stage. Grade III/IV thrombocytopenia, neutropenia, anaemia, febrile neutropenia requiring hospitalisation, non-hematologic toxicities were noted in 13 (12.8%), 18 (17.7%), 18 (17.7%), 1 (1%), 1 (1%), patients respectively. Complete Radiological response, partial response, Stable disease, progressive disease was seen in 6 (5.9%), 51 (50%), 23 (22.5%) 8 (8.7%), respectively. Resection was done in 29 (28.4%). Complete and partial pathological response were seen 19 (65.5%), 10 (34.4%), respectively. PFS at 40 and 80 weeks was 90%, 73%, respectively and OS at 80 weeks was 86%. PFS at 40 and 80 weeks was 100% and 90.5%, respectively with resection, while it was 86% and 65%, without resection (P value 0.015). OS at 40 and 80 weeks was 100% (both) with resection, while it was 96% and 79.5% weeks without resection. (p-value 0.034). CONCLUSIONS: Carbo/pacli based CRT is effective with acceptable toxicity profile in treating localised oesophageal cancer as both as Radical CRT and as a part of multimodality therapy. For definitive results, long term follow up and prospective analysis are required.

Impact of Time Interval Between Chemoradiation and Surgery on Pathological Complete Response and Survival in Rectal Cancer.

BACKGROUND: Limited data are available regarding the impact of time duration between chemoradiation (CRT) and surgery on pathological complete response (PCR). A PCR translates into better overall and disease free survival. The objective of this study was to determine effect of time duration on outcome after preoperative CRT in rectal cancer. MATERIALS AND METHODS: A retrospective review of patients undergoing operations for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided in two groups: Group 1 underwent surgery in ≤ 8weeks post neoadjuvant CRT and Group 2 after 8 weeks. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year overall survival and disease free survival was calculated using Kaplan Meier curves and significance was determined using the log rank test. RESULTS: There were 66 patients in group 1 and 93 in group 2. No significant difference in PCR was observed between the two. However, estimated 5 year DFS was significantly higher in Group 1 (66.7%) as compared to Group 2 (53.8%) (P=0.04). Estimated overall 5 year overall survival was not significantly different at 68.2% versus 54.3% (P= 0.09). CONCLUSIONS: Delaying surgery more than 8 weeks after preoperative CRT does not impact for PCR in rectal cancer.

Chemotherapy alone or combined chemotherapy and involved field radiotherapy in favorable risk early-stage classical Hodgkin lymphoma-a 10 years experience.

OBJECTIVE: To determine the outcome of patients with early-stage (stage I-II) favorable risk classical Hodgkin lymphoma treated with chemotherapy alone or combined modality treatment (CMT) utilizing chemotherapy and involved field radiotherapy. METHODS: This retrospective study was done at Department of Medical oncology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan from January 2004 to December 2013. RESULTS: There were 101 patients, with male predominance (71.3%). Mean age was 34 years. Sixty three (62.4%) patients received CMT and 38 (37.6%) patients had chemotherapy alone. Ninety eight percent patients had ABVD chemotherapy. Dose of radiotherapy ranged from 20 to 36 gray. Difference between baseline characteristics and major toxicities among the two groups was insignificant. Patients treated with CMT had better overall survival compared to chemotherapy alone: 100% versus 91% at five years and 96% versus 81% at 10 years, respectively (p=0.03). Progression free survival was also better with CMT against chemotherapy alone at five years (98% versus 81%) and 10 years (82% versus 71%) (p=0.01). CONCLUSION: Favorable risk classical Hodgkin lymphoma patients had better overall survival and progression free survival when treated with CMT against chemotherapy alone.

Characteristics And Outcome Of Patients With Diffuse Large B Cell Lymphoma-Treated With Chemotherapy Or Chemo-Immunotherapy.

BACKROUND: Diffuse large-B-cell lymphoma, is the most common subtype of Non-Hodgkin lymphoma. Aim of this study was to look at the characteristics and outcome of DLBCL patients who were treated with chemotherapy or chemotherapy plus rituximab at our institution. METHODS: Data of 750 patients, who got registered at our institute between 2007 and 2014, was reviewed retrospectively. After appropriate exclusions, 337 were included. Disease free survival (DFS) and overall survival (OS) were compared between patients who received rituximab plus CHOP (Cyclophosphamide, Doxorubicine, Vincristine, Prednisolon) (R-Ch) and standard chemotherapy- CHOP (S-Ch). RESULTS: Males and females were 216 (64%) and 121 (36%) respectively, with median age 38 years (Range 18-80 yrs.). R-Ch and S.Ch was received by 129(38.3%) and 197(58.4%) patients, respectively. Complete remission (CR) was achieved by 81 (62.8%) vs. 105 (53.3%) patients in R-Ch vs. S-Ch cohorts, respectively. In subset analysis CR was seen in 34 (63.0%) and 45 (58.4%) (p=0.01) in R-Ch/XRT and S-Ch/XRT, respectively. At three years, DFS was 85.3% vs. 74% (p=0.04) and OS was 82.2% vs. 72.6% (p=0.02) in R-Ch and S-Ch cohorts respectively. Deaths observed were 9 Vs.13 in R-Ch/XRT and S-Ch/XRT, respectively. CONCLUSIONS: Based on our study, onset of DLBCL is at younger age in our population with male predominance. Addition of rituximab to CHOP resulted in better DFS and OS in patients with DLBCL. In developing countries, due to cost, large number of patients do not have access to rituximab. Efforts should be made to reduce the price of targeted therapies so that more and more patients are benefitted from these newer agents.

Secondary malignant melanoma in primary mediastinal germ cell tumour.

Secondary transformation in Germ Cell Tumours (GCT) is an extremely rare event. We report here a case of malignant melanoma arising in primary mediastinal GCT. A young male presented with new onset dyspnoea and a mediastinal mass. As serum alpha fetoprotein was raised, a diagnosis of primary mediastinal GCT was made. He achieved remission with standard chemotherapy and resection of the mass. After a year, he relapsed with widespread disease which on work-up revealed malignant melanoma. As examination for cutaneous melanoma was unremarkable, a diagnosis of mediastinal GCT with secondary transformation to melanoma was made. Exact origin of melanoma in GCTs is unknown, but these may occur from transformation of dermal elements or de-differentiation of germ cells to melanomas. Before making such a diagnosis, search for primary cutaneous melanoma is mandatory. No clear guidelines exist in literature for the treatment of secondary melanomas, so current management guidelines for cutaneous melanoma may be followed.

Can induction chemotherapy before concurrent chemoradiation impact circumferential resection margin positivity and survival in low rectal cancers?

BACKGROUND: Distance from anal verge and abdominoperineal resection are risk factors for circumferential resection margin (CRM) positivity in rectal cancer. Induction chemotherapy (IC) before concurrent chemoradiation (CRT) has emerged as a new treatment modification. Impact of IC before concurrent CRT on CRM positivity in low rectal cancer remains to be independently studied. The objective of this study was to determine CRM positivity in low rectal cancer, with and without prior IC, and to identify predictors of disease free and overall survival. MATERIALS AND METHODS: Patients who underwent surgery for rectal cancer between 2005 and 2011 were retrospectively reviewed and divided into two groups. Group 1 received IC before CRT and Group 2 did not. Demographics, clinicopathological variables and CRM status were compared. Actuarial 5 year disease free survival (DFS), overall survival (OS) and independent predictors of survival were determined. RESULTS: Patients in the IC group presented with advanced stage (Stage 3=89.2% versus 75.4%) (P=0.02) but a high rate of total mesorectal excision (TME) (100% versus 93.4%) (P=0.01) and sphincter preservation surgery (54.9 % versus 22.9%) (P=0.001). Patients with low rectal cancer who received IC had a significantly low positive CRM rate (9.2% versus 34%) (P=0.002). Actuarial 5 year DFS in IC and no IC groups were 39% and 43% (P=0.9) and 5 year OS were 70% and 47% (P=0.003). Pathological tumor size [HR: 2.2, CI: 1.1-4.5, P=0.01] and nodal involvement [HR: 2, CI: 1.08-4, P=0.02] were independent predictors of relapse while pathological nodal involvement [HR: 2.6, CI: 1.3-4.9, P=0.003] and IC [HR: 0.7, CI: 0.5-0.9, P=0.02] were independent predictors of death. CONCLUSIONS: In low rectal cancer, induction chemotherapy before CRT may significantly decrease CRM positivity and improve 5 year overall survival.

Impact of lymph node ratio and number on survival in patients with rectal adenocarcinoma after preoperative chemo radiation.

BACKGROUND: Retrieval of <12 lymph nodes after proctectomy and preoperative chemoradiation (C-XRT) may improve survival in good risk patients. The objective of this study was to determine impact of <12 retrieved lymph nodes and lymph node ratio (LNR) on survival in a population with certain poor prognostic features for rectal cancer. METHODS: Patients who underwent surgery for rectal adenocarcinoma between 2005 and 2011 were divided them into <12 or >12 lymph node groups. The LNR groups were based on interquartile range. Clinicopathological and treatment outcomes were compared. Expected 5 year disease free and overall survival was calculated. Cox proportional hazard model was used to determine independent predictors. RESULTS: More patients in <12 lymph nodes removed group had low tumors (<5 cm from anal verge) (75.5% versus 60.7%) (P=0.03) and underwent abdominoperineal resection (59.1% versus 42.9%) (P=0.02). Overall survival (OS) and disease free survival (DFS) was not different [(56% and 52% (P=0.7)] [(50% and 57% (P=0.5)]. LNR<0.15 was independent predictor of DFS while LNR ratio<0.12 for OS on multivariate analysis. CONCLUSION: LNR and not number of retrieved nodes impacts survival in younger patients with predominance of anorectal tumors after C-XRT. A specific LNR cutoff remains to be defined.

Outcome of rectal cancer in patients aged 30 years or less in the Pakistani population.

BACKGROUND: The incidence of rectal cancer is increasing in younger age groups. Limited data is available regarding survival outcome in younger patients with conflicting results from western world. The goal of this study was to determine survival in patients with rectal cancer<30 years of age and compare it with their older counterparts in the Pakistani population. MATERIALS AND METHODS: A retrospective chart review of patients operated for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided into two groups, Group 1 aged ≤30 years and Group 2 aged >30 years. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year survival was calculated using Kaplan Meier curves and significance was determined using the Log rank test. RESULTS: There were 38 patients in group 1 and 144 in group 2. A significantly high number of younger patients presented with poorly differentiated histology (44.7% vs 9.7%) (p=0.0001) and advanced pathological stage (63.1% vs 38.1%) (p=0.04). Predicted overall 5 year survival was 38% versus 57% in groups I and II, respectively (p=0.05). Disease free survival was 37% versus 52% and was significantly different (p=0.007). CONCLUSIONS: Early onset rectal cancer is associated with poor pathological features and a worse outcome in Pakistani population.

Impact of acellular mucin pools on survival in patients with complete pathological response to neoadjuvant treatment in rectal cancer.

BACKGROUND: Rarely, patients with pathological complete response (PCR) after neoadjuvant chemoradiotherapy demonstrate acellular mucin pools. The prognostic significance of this finding is controversial. The objective of this study was to determine impact of acellular mucin pools on disease free and overall survival in patients with complete pathological response to neoadjuvant chemoradiotherapy in rectal cancer. METHODS: One hundred and seventy two patients received neoadjuvant chemoradiotherapy for rectal cancer and underwent surgery. Patients were divided into two groups based on presence of acellular mucin pools. Locoregional failures, distant failures and deaths were compared. Expected 5 year disease free and overall survival was calculated. RESULTS: Median follow-up was 36(4-94) months. Complete pathological response was identified in 35(20.3%) patients. Of these, 12(34.2%) had acellular mucin pools in resected specimen. Majority of mucin negative tumors were moderately differentiated (78% vs 25%) (P = 0.005). Median overall survival for mucin positive and mucin negative tumors was 4(1.3-5.7) and 3.3(0.1-6.3) years respectively. Expected 5 year disease free and overall survival for mucin positive and mucin negative tumors was 73% and 89% (P = 0.1) and 75% and 87% (P = 0.4). CONCLUSION: Acellular mucin pools in rectal cancer following a PCR to neoadjuvant treatment do not impact survival.

Patterns of care and outcomes of adult osteosarcoma in a tertiary care cancer centre in Pakistan.

OBJECTIVE: To present our experience of treatment outcomes in adult osteosarcoma patients. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data related to 74 adult patients with osteosarcoma from 1995 to 2009. The treatment plan consisted of surgery preceded by neo-adjuvant chemotherapy followed by adjuvant chemotherapy. SPSS 16 was used for statistical analysis. RESULTS: Of the 74 patients in the study, 58 (78%) were in the 18-29 age group with an overall male-to-female ratio of 3:1. The commonest site of disease was femur, 30 (43%). Of the 66 (89%) patients undergoing definitive surgery, 59 (89.4%) had amputation. The remaining 7 (10.6%) limb salvage operations were in the neo-adjuvant chemotherapy group. Good histopathological response rates in high-dose methotrexate containing regimens and other regimens were similar with an overall good response rate of 18/51 (35%). The commonest site of relapse was lung.Twelve out of 27 (44%) patients with lung-only metastases underwent successful metastatectomy. For patients with localised disease at presentation 3-year event-free survival was 30%, and 3-year overall survival was 71%. For patients with metastases at presentation 3-year overall survival was 45%. Median overall survival for patients receiving high-dose methotrexate and other regimens was 1.7 years vs 2.9 years. CONCLUSION: Adult osteosarcoma treated with cisplatin/doxorubicin based chemotherapy and surgery had good outcomes. The role of high-dose methotrexate in adult osteosarcoma remains uncertain.

Modification and implementation of NCCN guidelines on hepatobiliary cancers in the Middle East and North Africa region.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Hepatobiliary Cancers address hepatocellular cancer, cancer of the gallbladder, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma. Hepatocellular cancer incidence is higher in the Middle East and North Africa (MENA) region than in the West, and hepatitis B and C infections are particularly important; the incidence of gallbladder cancer is among the highest in the world. Regional problems include delay in diagnosis, shortage of trained staff, and insufficient liver transplant facilities. Furthermore, costs associated with molecular and targeted therapies are an increasing concern. A committee was formed, consisting of leading specialists and decision-makers from the region, with each member being tasked to suggest modifications to the existing guidelines based on review of the literature and consultations with local colleagues. This committee met as a group, and then continued to discuss and debate the suggested modifications electronically. Several recommendations were finalized after vigorous debate. The final approved recommendations were then presented in April 2009 to the chair of the NCCN Hepatobiliary Cancers Panel for onward transmission and approval. This project represents an effort to modify and implement the NCCN Guidelines on Hepatobiliary Cancers in the MENA region, while taking into consideration local differences in patient and disease characteristics. The hope is that this will form the basis of future local, regional, and international cooperation in guideline development and research.

Radiation-induced angiosarcoma of the breast shows major response to docetaxel after failure of anthracycline-based chemotherapy.

We report on the case of a patient with a diagnosis of an uncommon breast tumour, namely a radiation-induced angiosarcoma, which was primarily refractory to anthracycline-based chemotherapy, but highly sensitive to docetaxel. Although the sarcomas in general tend to be relatively refractory to taxanes, there is some evidence that the angiosarcomas may be sensitive to these agents. This is particularly well documented with paclitaxel, but may also be the case with docetaxel.