Neoadjuvant chemotherapy for locally advanced head and neck squamous cell carcinoma - Is it still relevant? A practice pattern survey among oncologists of India.

Objectives: Concurrent chemotherapy is the recommended treatment for locally advanced head and neck (H&N) squamous cell carcinoma, and neoadjuvant chemotherapy (NACT) is debated with a few special indications. NACT for advanced head and neck cancer has been studied in clinical trials for more than 2 decades without clear demonstration of the benefit for loco regional tumor control or overall patient survival. Its benefit remains controversial in the absence of clear evidence to define its role. However, there is widespread use of NACT among oncologists. We conducted an online survey to find out the frequency, pattern, prevalence, and aims for use of NACT in locally advanced head and neck cancers among radiation, medical, and surgical oncologists. Materials and Methods: Oncologists across India who expressed interest to participate in our survey were asked to complete a short online questionnaire designed to identify the current practice pattern of NACT in head and neck cancer. A mobile app-based questionnaire was sent to 200 oncologists across the country to assess the pattern of NACT use and to solicit their most frequent therapy approach for patients with locoregionally advanced head and neck cancer. Results: One hundred and fifty (150) oncologists completed and returned the survey (75%), and 130 were finalized (94 radiation oncologists, 19 medical oncologists, and 17 surgical oncologists). The single most common treatment approach reported for patients with locoregionally advanced H&N cancer was that of sequential chemoradiation (61%), specifically NACT with the TPF regimen (78.5%), followed by radiation therapy. The primary objectives cited by respondents for the use of NACT included the desire to buy time for definitive treatment (20%) and to achieve R0 resection (19.2%). Use of NACT in most patients was more preferred by medical oncologists (21.1%) and radiation oncologists (19.1%) than surgical oncologists (11.8%). Thus, there is not much difference in perception in practice of NACT in radiation, medical, and surgical oncologists. A minimum of two cycles of NACT was preferred by more than half of the doctors (55.4%) with 59.6% radiation oncologists using it before further assessment. Conclusion: Although level I evidence for inferior outcomes with NACT as compared to concurrent chemoradiation therapy is there, the use of NACT is quite common among various oncologists in the country because of reasons such as buying time for definitive treatment, achieving R0 resection, better outcome and survival, partial response, better tolerability, better distant control, LN size regression, down-staging of primary tumor, selection of chemosensitive patients, reducing the volume of the radiation field, and better tolerability of subsequent Chemoradiation (CTRT) intensity of subsequent chemoradiation therapy.

Comparison of twice weekly palliative RT versus continuous hypofractionated palliative RT for painful bone metastases.

Background: Palliative hypofractionated radiotherapy (RT) is an effective mode of treating painful bone metastasis. While 8 Gy single fraction radiation is often effective for the same, for complicated bone metastases a protracted fractionated regimen is preferred, of which 30 Gy/10#/2weeks or 20 Gy/5#/1 week are the most common worldwide. However such schedules add to the burden of already overburdened radiation treatment facilities in a busy center, wherein alternative logistic favourable schedules with treatment on weekends are preferred. Here we compare the efficacy of a twice weekly schedule to that of standard continuous 20 Gy/5 #/1 week schedule in terms of pain relief, response and quality of life. Materials and methods: A prospective non randomized study was undertaken from Jan 2018 to May 2019, wherein eligible patients of complicated bone metastases received palliative radiotherapy of 20 Gy/5#, either continuously for 5 fractions from Monday to Saturday or twice weekly, Saturday and Wednesday, starting on a Saturday over about 2 weeks. Pain relief was assessed by the Visual Analogue Scale (VAS) and FACES pain scale recorded prior to starting palliative RT and at 4 weeks, 3 months and 6 months. Results: Thirteen patients received continuous Hypofractionated RT while 16 received it in a twice weekly schedule. Spine was the most common site receiving palliative Radiation (27/29), while breast cancer was the most common primary (16/29). The demographic and the baseline characteristics were comparable. The mean pain score decline at 4 weeks was 2.56 ± 1.1 and 2.71 ± 0.52 in the 5-day and the two-week schedule, respectively (p = 0.67). Conclusion: A twice weekly schedule over about two weeks was found to be equivalent in pain control and response to the standard fractionated palliative radiation and, thus, can be safely employed in resource constrained, busy radiotherapy centers.

Pattern of locoregional failure in postoperative cases of locally advanced carcinoma of buccal mucosa treated with unilateral versus bilateral neck radiation: lesson learned from a basic practice setup.

Background: Carcinoma of buccal mucosa forms a sizeable percentage of the diagnosed oral cavity cancers in India. There is limited data on elective treatment of the contralateral neck for well-lateralized carcinoma with no involved nodes in the contralateral neck. We conducted this study to compare locoregional control in patients treated with unilateral vs. bilateral neck irradiation. Materials and methods: 48 patients with carcinoma of buccal mucosa were selected. Patients were divided into unilateral and bilateral arms based on radiation treatment of the ipsilateral or bilateral neck. All patients received adjuvant radiation with Cobalt 60 unit. Patient-specific and follow-up data were collected from records and dosimetric data from treatment planning system (TPS). Chi-square and unpaired t-test was used to compare data between arms and Kaplan Meier plot; Cox regression was used for survival analysis. Results: After a median follow-up of 23 months, 15 (31.3%) patients had developed disease recurrence, 8 and 7 in the unilateral and bilateral arms, respectively (p = 0.591). There was no contralateral neck failure during the follow-up period. The 2-year disease-free survival was 68.2% and 72.2% in the unilateral and bilateral arms, respectively. Among risk factors for disease recurrence, depth of invasion (DOI), delay in starting radiation and planning target volume (PTV) coverage were significant contributing factors. Cox multivariate regression suggested DOI and delay in starting radiation to be significant prognostic factors for disease-free survival (DFS). Conclusion: Bilateral neck radiation does not provide any advantage over ipsilateral neck radiation for properly selected well lateralized buccal mucosal squamous cell carcinoma. Ipsilateral neck radiation facilitates better sparing of organs at risk.

Dosimetric and clinical outcomes of CT based HR-CTV delineation for HDR intracavitary brachytherapy in carcinoma cervix - a retrospective study.

BACKGROUND: Brachytherapy for carcinoma cervix has moved from Point A based planning to optimization of dose based on HR-CTV. Guidelines have been published by GEC ESTRO on HR-CTV delineation based on clinical gynecological examination and MR sequences. These have given significant clinical results in terms of local control. However, many centers around the country and worldwide still use CT based planning, which restricts HR-CTV delineation, as disease and cervix can rarely be differentiated on a planning CT. Various studies have been done to develop CT based contouring guidelines from the available data, but enough evidence is not available on the clinical outcome when treatment is optimized to HR-CTV contoured on CT images. The purpose of this study is to find out the relation between local control and dosimetry of HR-CTV as delineated on CT images. MATERIALS AND METHODS: Patients of locally advanced carcinoma cervix treated radically with EBRT of 50 Gy in 25# and at least 4 cycles of concurrent weekly Cisplatin having a complete or partial response to EBRT were taken for study. All patients had completed CT based Intracavitary brachytherapy to 21 Gy in 3# of 7 Gy per # with dose prescription at point A and optimizing dose to reduce bladder and rectal toxicity. Follow up data on locoregional recurrence was obtained. HR-CTV delineation was done retrospectively on the treatment plan following guidelines by Viswanathan et al. EQD2 doses for EBRT+BT were calculated for point A and HR-CTV D90. The dosimetric data to HR-CTV and to Point A were then compared with patients with locoregional control and with local recurrence. RESULTS: 48 patients were taken, all had squamous cell carcinoma. The median age was 48 years. 33.33% were stage IIA, the rest were stage IIB. Median follow-up was 30 months with 25% developing recurrence of the disease. HR-CTV D90 EQD2 dose was significantly higher in patients with locoregionally controlled disease than in patients with local recurrence (83.97 Gy10 vs. 77.96 Gy10, p = 0.002). Patients with HR-CTV D90 EQD2 dose greater than or equal to 79.75 Gy 10 had better locoregional control than patients receiving dose less than 79.75 Gy10 (p = 0.015). Kaplan Meier plot for PFS showed significantly improved PFS for patients receiving HR-CTV D90 dose of at least 79.75 Gy10 (log-rank p-value = 0.007). Three year progression free survival was 87.1% in patients receiving HR-CTV D90 dose of at least 79.75 Gy10. CONCLUSION: CT based HR-CTV volume delineation with the help of pre brachytherapy clinical diagrams and MRI imaging may be feasible in a select subgroup of patients with complete or near-complete response to external beam radiation.

A dosimetric study of electron beam therapy vs. high-dose-rate mould brachytherapy in adjuvant treatment of non-melanoma skin carcinomas of the head and neck region.

PURPOSE: Radiation for superficial tumours of the head and neck region can be given either by brachytherapy or electrons. Brachytherapy (BT), due to rapid dose fall-off and minor set-up errors, should be superior to external beam radiotherapy (EBRT) for treatment of lesions in difficult locations such as the nose and earlobe. The present study is a dosimetric comparison of computed tomography (CT)-based mould brachytherapy treatment plans with 3D conformal electron beam therapy in the treatment of non-melanoma skin cancers (NMSC). MATERIAL AND METHODS: From December 2017 to November 2018 10 patients with NMSC of the head and neck region (forehead, nose, cheek) who underwent adjuvant radiation with HDR brachytherapy (BT) with a surface mould individual applicator were enrolled for analysis. We evaluated dose coverage by minimal dose to 90% of planning target volume (PTV, D90), volumes of PTV receiving 90-150% of prescribed dose (PD) (VPTV90-150), conformal index for 90% and 100% of PD (COIN90, COIN100), dose homogeneity index (DHI), dose nonuniformity ratio (DNR), and exposure of organs at risk (OARs) (eyes, lens, underlying bone and skin). Prospectively, we created CT-based treatment plans for electron beam therapy. We compared conformity (COIN90, COIN100), dose coverage of PTV (D90, VPTV90, VPTV100), volumes of body receiving 10-90% of PD (V10-V90), doses to OARs (D0.1cc and D2cc) of BT and electron plans. RESULTS: We obtained mean BT-DHI 0.81, BT-DNR 0.608, Electron-DHI 1.25. We observed no significant differences in VPTV90,100 and D90 between BT and electron beam. Mean BT-VPTV125,150 were significantly higher than Electron-VPTV100,125. COIN90 was superior for BT plans. CONCLUSIONS: CT-based surface mould brachytherapy results in better conformity of superficial lesions on small, irregular surfaces such as the nose and inner canthus than electrons with a slightly higher skin dose.

Treatment of locally advanced carcinoma cervix with special emphasis on brachytherapy: A practice pattern survey among young radiation oncologist of India.

BACKGROUND: Carcinoma cervix is one of the two most common cancers of Indian women with very high morbidity and mortality burden. Although India probably is the leading country in numbers patients of cervix treated radically with combination of teletherapy and brachytherapy (BT), there is presumed diversity of practice across the country due to the inequality of available infrastructure, absence of uniform the training of the radiation oncologists, and absence of any national guidelines. The present survey was conducted to determine current practice patterns in management of locally advanced carcinoma cervix with regard to gynecologic high-dose-rate among the radiation oncologist across the country. METHODOLOGY: A 25-item survey was undertaken to study the standard management pattern of Stage IIB-IIIB cervical cancer with special emphasis on the BT practice patterns among various young radiation oncologist working across the country. The survey was undertaken in person in the form of interview questionnaire among the younger members of association of radiation oncologist of India during two national conferences, along with telephonic interview of other members as obtained from the national directory. RESULTS: About 57 young radiation oncologists from 57 centers across the country were surveyed. 25 of them represented private nonacademic centers, 24 represented government academic centers, the rest were from private academic, nongovernmental organization (NGO) run and other centers. The most common teletherapy dose prescribed was 46 Gy/23# for Stage II, and50 Gy/25 # for Stage III disease. HDR after loader with 192Ir is the most common machine (82.6%) in use and computed tomography scan is the most commonly (30/57) used imaging for planning. The most common intracavitary dose pattern for all stages was 7 Gy × 3 fractions (30/57s) and 9 Gy × 2 (12/57) fractions. Although in most centers, computed tomography-based delineation of organs at risk is done routinely; however, target volume delineation and dose prescription/optimization for the same is routinely done in handful of centers (5/57). The mean planned dose to Point A for combined external-beam radiation and BT (EQD210) was about 77.5 Gy for Stage IIIB and 72.6 Gy for Stage II disease. CONCLUSION: Although fractionation patterns may vary, the overall mean dose administered for cervical cancer is similar across the country, which is slightly lower than the recommended doses as per stage by various international guidelines.

Pattern of Failure with Locally Advanced Cervical Cancer­ A Retrospective Audit and Analysis of Contributory Factors

Background: The majority of the global burden of cervical cancer is affecting developing countries. Despite improvement in treatment of patients presenting at a locally advanced stage, approximately 50% experience recurrence within the 1st two years. This study was conducted to analyse contributory factors for recurrence within 24 months. Methods: The present retrospective study was undertaken to analyse factors affecting recurrence, type of failure and the follow up pattern of patients who completed treatment with a minimum follow-up period of 6 months during the study period of 5 years. Results: Out of 323 patients included in the study, 112 (34.7%) presented with recurrence within the follow-up period. The stage and histology had a significant impact on disease free survival (DFS). Of those who were followed-up regularly, recurrence was observed in 28.7% with a DFS of 81.3 months, in contrast to the 48. 5% patients with a DFS of 45.0 months for whom follow-up was irregular. The failure pattern was mostly in the form of nodal recurrence (61%). On univariate analysis, treatment time, EBRT and ICBT gap and mean EQD2 point A were found to associated with a better outcome in terms of 2yr DFS. On Cox regression analysis, stage, histology, treatment gap (HR-0.48) and follow up pattern (HR-0.24) retained their effects on survival. Point A dose was higher in patients without recurrence (P value 0.000) unlike other assymmetric parameters. Conclusion: Apart from point A cumulative dose (mean EQD2), stage, histology and treatment gap were the factors that affected early local failure. An interesting result was that follow-up pattern had a significant impact on DFS period.

Pulmonary blastoma in a child: Report of a case with cytological findings.

Pulmonary blastoma is an uncommon tumour. It constitutes <0.1% of all resected lung cancers. It is even more rare in children with only a few case reports describing this entity in them. Pulmonary blastoma should not be confused with pleuropulmonary blastoma which is a paediatric lung tumour with different morphology and better outcome. Here we take the opportunity of describing pulmonary blastoma in a 3 years old child along with its cytological findings.

Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy.

Primary adenocarcinoma of duodenum is a very rare tumour with a prevalence of only 0.3 to 1% of among all the tumours of gastrointestinal tracts. Localised tumours, if resected have good prognosis but those with metastates entails a poor prognosis, where generally palliation may be the only feasible option. Low dose continous cytotoxic treatment or metronomic chemotherapy prevents neoangiogenesis and chemoresistance thereby, provides excellent symptom relief and palliation in many advanced heavily pretreated solid malignancies. It offers as an affordable, less toxic therapy with moderate to good efficacy. Here we report a case of a 52 year female who, presented with history of maleana, pallor and pedal edema for last 2 months. Her performance status was poor (KPS 40) and she had enlarged left supraclavicular lymph node, palpable liver and vague mass in paraumbilical region. Upper GI endoscopy revealed large ulceroproliferative growth in the D2 segment and HPE showed moderately differentiated adenocarcinoma. CT scan revealed paratracheal and retroperitoneal lymphadenopathy and bone scan revealed vertebral metastasis. Patient received oral cyclophosphamide and hematinic and vitamin support, along with radiation to spine. There was near complete clinical response, and progression free period of about 32 weeks. Thus, single agent cyclophosphamide in the present case provided near total clinical response and prolonged period of freedom from disease progression with excellent palliation of symptoms. Hence in patient of advanced and metastatic small bowel cancer, with poor performance status metronomic therapy with single agent cyclophosphamide may provide viable option both for treatment and palliation.

Malignant acrospiroma of chest and abdominal wall treated with chemotherapy.

Acrospiroma denotes a group of benign ductal tumours of the eccrine sweat glands that may or may not be connected to the skin. Although various eccrine sweat gland tumours including benign acrospiroma are widely reviewed, malignant acrospiroma is rarely reported. Malignant acrospiroma have the propensity to recur locally and metastasizes to regional lymph nodes. The primary treatment is wide local excision with or without lymph node dissection. Local radiation is added in the presence of high risk features to reduce the risk of recurrence. We describe a case of a malignant acrospiroma involving wide areas of chest and abdominal wall with metastases to bilateral axillary lymph nodes in a 47 year old man showing minimal clinical response to combination chemotherapy and paclitaxel.

Oncology knowledge gap among freshly passed interns in a Government Medical College of Eastern India.

OBJECTIVES: A survey was conducted among freshly passed undergraduate doctors of a medical college in Eastern India with the aim to investigate their exposure to oncology patients, their knowledge about various aspects of oncology patient management and their confidence in managing patients with cancer. MATERIALS AND METHODS: One hundred and twelve newly passed interns of a Government Medical College in Kolkata were interviewed using semi-structured partly open ended and partly closed end questionnaire. The questionnaire dealt with the qualitative and quantitative aspects of knowledge and perception of the interns about the problem of cancer and its management. RESULTS: A total of 82 interns responded to the questionnaire, with a response rate of 73.2%. About 53% of the respondents have seen less than five patients during their undergraduate ward/clinical postings. Among the respondents, 71% felt they were confident in diagnosing cancer, and about 56% were confident in counseling of patient and their relatives about cancer. About 63% were aware about the role of surgery; however, only 32% and 37.5% were aware about the role of radiotherapy and chemotherapy, respectively. A dismal 12.5% were confident of care of terminal and late stage patients. Preparedness was correlated with exposure to patients with cancer (P = 0.03). Majority (87%) felt the need for incorporating oncology training at the undergraduate level and the most frequent method (67%) suggested for doing so was having separate posting in radiotherapy department/oncology wards. CONCLUSION: There is glaring knowledge gap among newly passed doctors and integrated oncology postings during undergraduate training and during internship may help seal this gap.

Single Fraction versus Multiple Fraction Radiotherapy for Palliation of Painful Vertebral Bone Metastases: A Prospective Study.

CONTEXT: Metastatic bone disease is a commonly encountered problem in oncology practice. The most useful and cost effective treatment is radiotherapy (RT). Different fractionation schedule of RT can be used to treat such condition. AIMS: Assessment of pain response in patients with vertebral bone metastasis after treating them with various radiation fractionations and to compare the toxicity profile in the treatment arms. SETTINGS AND DESIGN: A prospective randomized study was designed to include total 64 patients from July 2010 to May 2011. Patients with histopathologically proven primary malignancy having symptomatic secondary deposits to vertebra were selected for the study. Patients were randomized to two arms receiving multiple fraction of RT with 30 Gy in 10 fractions and 8 Gy in single fraction RT, respectively. MATERIALS AND METHODS: Patients with age >75 years, Karnofsky Performance Status (KPS) <40, features of cord compression were excluded from study. Initial pain response was assessed using Visual Analogue Scale (VAS) and compared using the same scale at weekly interval up to 1 month after treatment completion. RESULTS: Arm A comprised of 33 patients while 31 patients were enrolled in Arm B. Baseline patient characteristics were comparable. Eleven patients were lost to follow-up. Initial pain scores were 7.23 ± 0.765 and 7.51 ± 0.55 in arm A and arm B, respectively. Pain scores reduced significantly in both the arms after 1 month (4.39 ± 1.82 in arm A; 5.25 ± 2.39 in arm B). Time of initiation of pain response was earlier in arm A (P = 0.0281), statistically significant. Mild G-I toxicity was noted in both the arms but differences in two arms were not statistically significant (P = 0.49), no interruption of treatment was required because of side effects. CONCLUSIONS: Different fractionation of radiation has same response and toxicity in treatment of vertebral bone metastasis. Single fraction RT may be safely used to treat these cases as this is more cost effective and less time consuming. Studies may be conducted to find out particular subgroup of patients to be benefitted more by either fractionation schedule; however, our study cannot comment on that issue.