Reirradiation with IMRT for recurrent head and neck cancer: A single-institutional report on disease control, survival, and toxicity.

AIM: To study and explores the feasibility and efficacy of re-irradiation (Re-RT) for locally recurrent head and neck cancer (HNC) and second primary (SP) malignancies. BACKGROUND: The most common form of treatment failure after radiotherapy (RT) for HNC is loco-regional recurrence (LRR), and around 20-50% of patients develop LRR. Re-irradiation (Re-RT) has been the primary standard of care in the last decade for unresectable locally recurrent/SP HNC. MATERIALS AND METHODS: It was a retrospective analysis in which we reviewed the medical records of 51 consecutive patients who had received Re-RT to the head and neck region at our institute between 2006 and 2015. RESULTS: Forty-eight patients were included for assessment of acute and late toxicities, response evaluation at 3 months post Re-RT, and analyses of locoregional control (LRC) and overall survival (OS). The median LRC was 11.2 months, and at 2 and 5 years the LRC rates were 41% and 21.2%, respectively. A multivariate analysis revealed two factors: initial surgical resection performed prior to Re-RT, and achievement of CR at 3 months after completion of Re-RT to be significantly associated with a better median LRC. The median OS was 28.2 months, and at 1, 2, and 5 years, OS were 71.1%, 55.9% and 18%, respectively. A multivariate analysis revealed initial surgical resection performed prior to Re-RT, and achievement of CR at 3 months post completion of Re-RT being only two factors significantly associated with a better median OS. Acute toxicity reports showed that no patients developed grade 5 toxicity, and 2 patients developed grade 4 acute toxicities. CONCLUSION: Re-RT for the treatment of recurrent/SP head and neck tumors is feasible and effective, with acceptable toxicity. However, appropriate patient selection criteria are highly important in determining survival and treatment outcomes.

Comparison between weekly cisplatin-enhanced radiotherapy and cetuximab-enhanced radiotherapy in locally advanced head and neck cancer: first retrospective study in Asian population.

AIM: To present a direct comparison between chemotherapy-enhanced radiotherapy (CERT) and biotherapy-enhanced radiotherapy (BERT) in locally advanced head and neck cancer. METHODS: It is a retrospective analysis of 53 patients with locally advanced head and neck cancer treated from August 2006 to December 2008. For CERT, patients received weekly cisplatin (40 mg/m2 ) and for BERT, a loading dose of 400 mg/m2 of cetuximab given one week prior to radiotherapy followed by 250 mg/m2 given weekly along with radiotherapy. Disease-free survival (DFS) and overall survival (OS) were computed with Kaplan-Meier curve with log-rank test for comparison between the two groups. Multivariate Cox proportional hazards regression analysis was performed to estimate the impact of known relevant prognostic factors on DFS and OS. RESULTS: The median DFS was significantly better with CERT than BERT group (50.82 vs 11.66 months; P = 0.031). The 3 years DFS was significantly higher in CERT group than in BERT group (60.0% vs 14.3%; P = 0.022). The median OS was significantly better with CERT than BERT group (53.61 vs 32.55 months; P = 0.044). The 3 years OS was also significantly higher in CERT group than in BERT group (74.0% vs 42.1%; P = 0.032). There were no significant differences in acute toxicities of all grade and grade ≥3 between the two groups. The compliance to treatment and assisted feeding dependency for more than 6 months duration were also not significantly different. CONCLUSION: CERT is associated with better outcome with no significantly increased acute toxicities compared to BERT.

Tumour volumes: Predictors of early treatment response in locally advanced head and neck cancers treated with definitive chemoradiation.

AIM: To analyse and predict early response 3 months post definitive chemoradiation (CCRT) utilising tumour volume (TV) measurement in locally advanced head and neck cancers (LAHNC). BACKGROUND: LAHNC are 3-dimentional lesions. The largest diameter of these tumours measured for T-classification may not necessarily reflect the true tumour dimensions. TV accurately reflects the tumour burden because it is a measurement of tumour burden in all three dimensions. MATERIALS AND METHODS: It is a single institutional prospective study including 101 patients with LAHNC treated with definitive CCRT. TV data noted were primary tumour volume (PTV), total nodal volume (TNV) and total tumour volume (TTV). Response evaluation was done at 3 months after the completion of definitive CCRT and patients were categorised either having achieved complete response (CR) or residual disease. RESULTS: Patients who had not achieved CR were found to have larger TV compared with those who had achieved CR. There were significant inverse correlations between PTV and response (median 16.37 cm(3) vs. 45.2 cm(3); p = 0.001), and between TTV and response (median 36.14 cm(3) vs. 66.06 cm(3); p < 0.001). Receiver operating characteristic (ROC) analysis identified an "optimal cut-off" value of 41 cm(3) for PTV and 42 cm(3) for TTV above and below which the magnitude of difference in response was the greatest. CONCLUSIONS: If response evaluation 3 months post CCRT is to be predicted it is simply not enough to measure the largest single dimension of the tumour. TV seems to be a better and more accurate reflection of the true total tumour burden or extent of the disease.

Dosimetric impact of setup errors in head and neck cancer patients treated by image-guided radiotherapy.

To assess and analyze the impact of setup uncertainties on target volume coverage and doses to organs at risk (OAR) in head and neck cancer (HNC) patients treated by image-guided radiotherapy (IGRT). Translational setup errors in 25 HNC patients were observed by kilovoltage cone beam computed tomography (kV CBCT). Two plans were generated. Plan one - the original plan which was the initially optimized and approved plan of the patient. All patients were treated according to their respective approved plans at a defined isocenter. Plan two - the plan sum which was the sum of all plans recalculated at a different isocenter according to setup errors in x, y, and z-direction. Plan sum was created to evaluate doses that would have been received by planning target volume (PTV) and OARs if setup errors were not corrected. These 2 plans were analyzed and compared in terms of target volume coverage and doses to OARs. A total 503 kV CBCT images were acquired for evaluation of setup errors in 25 HNC patients. The systematic (mean) and random errors (standard deviation) combined for 25 patients in x, y, and z directions were 0.15 cm, 0.21 cm, and 0.19 cm and 0.09 cm, 0.12 cm, and 0.09 cm, respectively. The study showed that there was a significant difference in PTV coverage between 2 plans. The doses to various OARs showed a nonsignificant increase in the plan sum. The correction of translational setup errors is essential for IGRT treatment in terms of delivery of planned optimal doses to target volume.

Impact of Adaptive Radiotherapy on Locally Advanced Head and Neck Cancer - A Dosimetric and Volumetric Study.

UNLABELLED: Objective of the study is to evaluate volumetric and dosimetric alterations taking place during radiotherapy for locally advanced head and neck cancer (LAHNC) and to assess benefit of replanning in them. MATERIALS AND METHODS: Thirty patients with LAHNC fulfilling the inclusion and exclusion criteria were enrolled in a prospective study. Planning scans were acquired both pre-treatment and after 20 fractions (mid-course) of radiotherapy. Single plan (OPLAN) based on initial CT scan was generated and executed for entire treatment course. Beam configuration of OPLAN was applied to anatomy of interim scan and a hybrid plan (HPLAN30) was generated. Adaptive replanning (RPLAN30) for remaining fractions was done and dose distribution with and without replanning compared for remaining fractions. RESULTS: Substantial shrinkage of target volume (TV) and parotids after 4 weeks of radiotherapy was reported (p<0.05). No significant difference between planned and delivered doses was seen for remaining fractions. Hybrid plans showed increase in delivered dose to spinal cord and parotids for remaining fractions. Interim replanning improved homogeneity of treatment plan and significantly reduced doses to cord (Dmax, D2% and D1%) and ipsilateral parotid (D33%, D50% and D66%) (p<0.05). CONCLUSIONS: Use of one or two mid-treatment CT scans and replanning provides greater normal tissue sparing alongwith improved TV coverage.

Retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients: A single institutional study.

AIM: To present a retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients at our institute. METHODS: Thirty-one patients of head and neck cancer who presented with a locoregional recurrence from April 2007 to April 2012 underwent salvage reirradiation. Median dose of first-time radiation was 70 Gy. Median duration of gap between the first and second course of radiation was 45.6 months. The median dose of reirradiation was 60 Gy. Conformal radiotherapy technique in the form of intensity modulated radiotherapy was used in 60% (17) of patients. Fourteen patients received concurrent chemotherapy or immunotherapy. RESULTS: After a median follow-up of 20.6 months, 12 patients were alive with no evidence of disease. The 3-year disease-free survival and overall survival were 28.7 and 48.5%, respectively. Acute and late toxicities were reported in 29 and 61% of patients, respectively. Severe grade 3 and 4 late complications were observed in nine patients but none of them led to mortality. CONCLUSION: Reirradiation appears to be both feasible and well tolerated in patients treated with previous radiotherapy for recurrent and second primary head and neck cancer. Careful case selection for reirradiation based on patient's performance status and tumor characteristics is essential.

Statistical modelling and forecasting of cervix cancer cases in radiation oncology treatment: a hospital based study from Western Nepal.

BACKGROUND: To estimate the numbers and trends in cervix cancer cases visiting the Radiotherapy Department at Manipal Teaching Hospital, Pokhara, Nepal, statistical modelling from retrospective data was applied. MATERIALS AND METHODS: A retrospective study was carried out on data for a total of 159 patients treated for cervix cancer at Manipal Teaching Hospital, Pokhara, Nepal, between 28th September 2000 and 31st December 2008. Theoretical statistics were used for statistical modelling and forecasting. RESULTS: Using curve fitting method, Linear, Logarithmic, Inverse, Quadratic, Cubic, Compound, Power and Exponential growth models were validated. Including the constant term, none of the models fit the data well. Excluding the constant term, the cubic model demonstrated the best fit, with R2=0.871 (p=0.004). In 2008, the observed and estimated numbers of cases were same (12). According to our model, 273 patients with cervical cancer are expected to visit the hospital in 2015. CONCLUSIONS: Our data predict a significant increase in cervical cancer cases in this region in the near future. This observation suggests the need for more focus and resource allocation on cervical cancer screening and treatment.

Chemoradiotherapy in the management of locally advanced squamous cell carcinoma esophagus: is surgical resection required?

PURPOSE: The present study aims to evaluate benefit of adding surgery to chemoradiotherapy alone in management of carcinoma esophagus. METHODS: We retrospectively analyzed 45 eligible patients of squamous cell esophageal carcinoma which were enrolled from February 2008 to April 2009. All patients were treated with chemoradiotherapy (50.40 Gy with 40 mg/m(2) of weekly cisplatin). Tumor response was assessed after 6 weeks of treatment. Patients with resectable disease were subjected to surgical resection (arm A) and remaining was kept on regular clinical follow-up (arm B). Overall survival (OS) was selected as the primary endpoint. The secondary end points were disease-free survival (DFS) and clinical toxicities. RESULTS: Median follow-up was 13.6 months. Pathological complete response was seen in 60.9 % patients in arm A. In arm B, 77.3 % patients attained radiological complete response (p = 0.194). The median OS was 16.4 and 19.1 months (p = 0.388) and median DFS was 5.8 and 4.1 months (p = 0.347) in arm A and B, respectively. The 2-year survival probability was 39.1 and 36.4 % (p = 0.387) in arm A and B, respectively. The recurrence probability was 56.5 % (SE = 5.6 %) and 45.5 % (SE = 4.2 %) (p = 0.328) in arm A and B, respectively. The probability of loco regional recurrence was more in arm B than in arm A (p = 0.002). CONCLUSIONS: The study suggests that there is no difference in clinical toxicity profiles or survival outcomes with either definitive chemoradiotherapy or chemoradiation followed by surgery in management of locally advanced esophageal cancer.

Clinicopathological profile of head and neck cancers in the Western development region, Nepal: a 4-year snapshot.

Regional cancer epidemiology is an important basis for determining the priorities for cancer control in different countries worldwide. There is no reliable information about the pattern of head and neck cancer in western Nepal and hence an attempt was here made to evaluate the situation based on hospital data, which provide the only source in the western region of Nepal. A clinicopathological analysis of head and neck cancers treated between 2003 and 2006 in Manipal Teaching Hospital affiliated to Manipal College of Medical Sciences, Pokhara, Western Development Region, Nepal was performed. A total of 105 head and neck cancer cases were identified with a male to female ratio of 1.8:1. The median ages of male and female patients were 62 and 64 years, respectively. Ninety-seven (92.4%) of the cancer patients were suffering from carcinoma, three (2.9%) had blastoma, three (2.9%) had sarcoma, and two (1.9%) had lymphoma. The majority (61.9%) of carcinoma cases were squamous cell carcinoma followed by anaplastic carcinoma (7.2%). Of the carcinoma cases, the most common site of primary lesion was larynx (19.6%), followed by the thyroid (14.4%), the tongue and hypopharynx with 10.3% cases each. Comparative analysis among males and females did not reveal any sex difference in type of head and neck cancers. The head and neck cancer pattern revealed by the present study provides valuable leads to cancer epidemiology in western Nepal and useful information for health planning and cancer control, and future research in western Nepal.

A quantitative comparison of gross tumour volumes delineated on [18F]-FDG PET-CT scan and CECT scan in head and neck cancers.

PURPOSE: To compare quantitatively Gross tumor volume (GTV), both primary and nodal areas of head and neck cancers, delineated on [18F]-2fluoro, 2deoxy d-glucose-positron emission tomography/computed tomography ([18F]-FDG-PET-CT) scan to those delineated on Contrast-enhanced CT scan (CECT scan). METHODS: A total of 26 consecutive patients with squamous cell cancers of head and neck were included in this study. The primary sites were oropharynx (n = 7), hypopharynx (n = 6), paranasal sinus (n = 6), nasopharynx (n = 4), oral cavity (n = 2), and one with unknown primary and secondary neck node. All patients underwent routine staging work-up. FDG-PET and CECT scans were performed with dedicated PET-CT scanner in single session as a part of the radiotherapy treatment planning for Intensity modulated radiotherapy/Image-guided radiotherapy. RESULTS: All patients had abnormal increased uptake in PET-CT scans. PET-CT resulted in changes of CT-based staging in 8 of 26 patients (up-staged in 7 and down-staged in 1). The mean primary and nodal GTV volumes on PET-CT and CT were significantly different (primary: PET-GTV: 48.43 ± 53.21 cc vs. CT 54.78 ± 64.47 cc, P < 0.001; nodes: PET-GTV: 12.72 ± 15.46 cc vs. 11.04 ± 14.87 cc, P < 0.001). The mismatch between two target volumes was statistically significant (P = 0.03 for GTV primary, P = 0.04 for GTV node). CONCLUSION: Accuracy of delineation of GTV can be improved along with functional imaging using [18F]-FDG. These metabolically active volumes are significantly smaller than CT-based volumes and could be missed during conventional CT-based target delineations of GTVs.

Cancer pattern in Western Nepal: a hospital based retrospective study.

Information on cancer patterns is an important basis for determining the priorities for cancer control in different countries worldwide. There is no reliable information about the incidence or pattern of cancer in Nepal and hence an attempt was made to assess the situation based on hospital data which is the only source in the western region of Nepal. Cancer cases diagnosed by all methods or treated in Manipal Teaching Hospital, affiliated to Manipal College of Medical Sciences, Pokhara, during 1st January 2003 to 30th May 2005 were used for the present study. A total of 957 cancer cases were identified with a male to female ratio of 1.1:1. The median age of male and female patients was 63 and 60 years, respectively. The proportion of microscopically confirmed cases, both from primary and metastatic sites was 87.5% and tobacco-related cancers constituted 48% of all cancers among males and 28% among females. For males the leading cancer sites were lung (22.2%), larynx (9.8%) and stomach (9%) and that for females was lung (20%), cervix (19.7%) and breast (7.8%). Among males, 33.1% of all cancers were in the respiratory system followed by digestive organ cancers (23.2%). Among females, 28.4% cancers were related to the reproductive system, 22.8% to the respiratory system and 14.1% to digestive organs. The cancer pattern revealed by the present study provides valuable leads to cancer epidemiology in Nepal, particularly in the western region, and provides useful information for health planning and future research.

Survey of palliative care concepts among medical students in India.

BACKGROUND: Students must develop a "tension for change" before new material is learned. Therefore, a needs assessment generally precedes curriculum change in order to identify what the target population thinks they already know about a subject. Undergraduate medical education in India is a 4(1/2) -year course. This is followed by a 1-year internship before the new physician can practice independently. AIM: To assess the level of awareness in palliative care concepts among final-year students at Kasturba Medical College, Manipal, India. MATERIALS AND METHODS: One hundred eleven final-year students participated in a survey study 6 months before graduation. The data were collected after the survey and the responses were analyzed. RESULTS: The reported theoretical knowledge of palliative care concepts was better than the level of confidence in performing practical aspects of palliative care. CONCLUSION: Before this survey, we hypothesized that medical students in India would have low levels of self-reported understanding of palliative care and its components. In contrast, they reported a high level of understanding of palliative care but very little understanding and confidence in performing the associated skills. From this, we conclude that these medical students are ready for instruction in the practical skills of palliative care.

Survey of palliative care concepts among medical interns in India.

BACKGROUND: Medical knowledge, if theoretical, will fade away if not reinforced especially if not clinically implemented. We conducted a survey study amongst interns to assess awareness and confidence of common palliative care issues. Undergraduate medical education in India is a 4(1/2) -year course. This is followed by a 1-year internship before the new physician can practice independently. AIM: To compare the level of awareness in palliative care concepts among interns to that of final-year medical students at Kasturba Medical College, Manipal, India. MATERIALS AND METHODS: Forty-four interns participated in a survey study. The data were collected after the survey and the responses were analyzed. We compared these data with those obtained from conducting the same survey among medical students. RESULTS: The reported theoretical knowledge of palliative care concepts was better than the level of confidence in performing practical aspects of palliative care. The interns, overall, did not out-perform the students. CONCLUSION: Before this survey, we hypothesized that interns in India would have low levels of self-reported understanding of palliative care and its components. We were hoping to see an improvement in knowledge and confidence with training. In contrast, there was not much of an improvement but rather a decline in some areas. From this, we conclude that when medical students become interns, they need reinforcement of knowledge and more hands-on experience.