Barriers in conducting clinical trials in oncology in the developing world: A cross‑sectional survey of oncologists.

BACKGROUND: Several obstacles impede oncologists from performing clinical trials in the developing world. This study aimed to identify these barriers in order of importance and suggest possible remedial measures. MATERIALS AND METHODS: Design – cross‑sectional survey. Two part questionnaire capturing experience of oncologists in practice and conducting trials (Part 1) and perceived barriers pertaining to investigator (training, time), patient (strict follow‑up protocol), infrastructure (funds) and professional environment (encouragement from seniors) (Part 2) were administered to oncologists in two different settings: (1) Online portal (Survey Monkey) (2) In person during a national conference (Best of American Society of Clinical Oncology). Responses were captured on a Likert scale (1–5). RESULTS: (436/3021) 14.04% responded. A total of 313 (71.8%) had experience in conducting trials, but these were mainly industry‑sponsored or small nonpractice changing studies. Lack of patient follow‑up was the most significant barrier (inter quartile range [IQR] 4–5) followed by inadequate training, time and funds (IQR 2–5) and lack of encouragement (IQR 2–4) in decreasing order of frequency. Lack of adequate training was a barrier across all specialties (113 [71.97%] radiation oncologists, 71 [60.68%] medical oncologists and 73 [71.56%] surgical oncologists). More than half of the respondents without experience in clinical trials worked in academic institutions (50.48%). They perceived time constraint as a barrier more than their counterparts into private practice (175/242 [72.31%] vs. 119/177 [66.47%] respectively). CONCLUSION: Inability to maintain patient follow‑up, lack of protected time and funds, inadequate training were the most significant barriers. Most of these can be addressed.

Practice of stereotactic body radiotherapy in a developing country: Perception, aspiration, and limitation ‑ A survey.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an effective and established modern technology now used more commonly. Radiation oncology personnel’s (ROP) opinion toward SBRT in the developing countries like India is unknown. SUBJECTS AND METHODS: A 30 question survey evaluating ROP’s profile, technological details, and SBRT’s perceptive were seeked. Tata Memorial Center – ROP’s email database was used. RESULTS: Survey questionnaire was emailed to 500 ROP’s and 224 ROP’s were contactable. Majority of the responders were from corporate hospitals and half of responders had experience of 5 or more years of experience in radiation oncology. SBRT was practiced by 70% of responders and the majority had adopted SBRT in 2010 or later. Quick turn around time, high dose delivery and competitive market forces were major factors to adopt SBRT. Lung was the most common site practiced followed by prostate, spine, and liver. All SBRT users were keen to increase SBRT in practice and the majority of non‑responders were planning to adapt SBRT in the recent future. Almost half of SBRT users were willing to share data and expertise for training others. Lack of infrastructure was the prime reason for not practicing SBRT. ROP’s perceived physics, radiobiology as the biggest challenge in SBRT. International collaboration may be helpful. CONCLUSION: Use of SBRT is expected to increase in India. Limited experience with lack of infrastructure in public funded centers is a major limitation. Unmet need of infrastructure, training and guidelines is enormous and formulation of Indian SBRT consortium will help reforming at all levels.

Optimizing treatment and analysis of prognostic factors for locally advanced nonsmall cell lung cancer in resource‑limited population.

BACKGROUND: Lung cancer most commonly presents in advanced stages in developing countries, where combined modality treatment using chemo‑radiotherapy (CTRT) is the standard of care. MATERIALS AND METHODS: A retrospective audit of patients of nonsmall cell lung cancer (NSCLC) treated at a single Institute from January 2008 to December 2012 was conducted. Various prognostic factors affecting disease‑free survival (DFS) and overall survival (OS) were studied by univariate and multivariate analysis. All patients were meticulously followed‑up clinically and telephonic contacts. RESULTS: Overall 171 patients of NSCLC were treated with definitive CTRT using concurrent chemotherapy in 66% patients and sequential therapy in 28% patients. The actuarial 2 years DFS was 17.5% and 2 years OS was 61.5%. Complete response to treatment resulted in significantly better DFS and OS. Definitive CTRT was very well‑tolerated in these patients with good compliance. CONCLUSION: Definitive CTRT, sequence being individualized depending on performance status and disease stage at presentation, is a feasible and effective treatment modality for locally advanced NSCLC patients in the developing world. Response to treatment is an important prognostic factor for treatment outcomes.

Factors predicting 'time to distant metastasis' in radically treated head and neck cancer.

Context: Various studies have shown the important risk factors for distant metastasis in head and neck cancer (HNC) which are present in most of the patients in developing countries. Identification of factors on the basis of time to distant metastasis (TDM) can help in future trials targeting smaller subgroups. Aims and Objectives: To identify the factors that predict TDM in radically treated HNC patients. Settings and Design: Retrospective audit. Materials and Methods: Retrospective audit of the prospectively maintained electronic database of a single HNC radiotherapy clinic from 1990 to 2010 was done to identify radically treated patients of HNC who developed distant metastasis. Univariate and multivariate analysis were done to identify baseline (demographic, clinical, pathological, and treatment) factors which could predict TDM, early time to metastasis (ETM; <12 months), intermediate time to metastasis (ITM; 12-24 months), and late time to metastasis (LTM; >2 years) using Kaplan Meier and Cox regression analysis, respectively. Results: One hundred patients with distant metastasis were identified with a median TDM of 7.4 months; 66 had ETM, 17 had ITM, and 17 had LTM. On multivariate analysis, the nodal stage 2-3 (N2/3) was the only baseline factor independently predicting TDM, ETM, and ITM, whereas none of the baseline factors predicted LTM. Conclusions: Higher nodal burden (N2/3) is associated with both ETM and ITM, and calls for aggressive screening, systemic therapy options, and surveillance. It is difficult to predict patients who are at a risk of developing LTM with baseline factors alone and evaluation of biological data is needed.

Thymoma: First large Indian experience.

BACKGROUND: Thymoma is the most common tumor of the anterior mediastinum. Surgery is mainstay of treatment, with adjuvant radiation recommended for invasive thymoma. Because of rarity, prospective randomized trials may not be feasible even in multicentric settings hence the best possible evidence can be large series. Till date Thymoma has not been studied in Indian settings. MATERIALS AND METHODS: All patients presenting to Thoracic disease management group at our Centre during 2006‑2011 were screened. Sixty two patients’ with histo‑pathological confirmation of thymoma medical records could be retrieved and are presented in this study. Mosaoka staging and WHO classification was used. The clinical, therapeutic factors and follow up parameters were recorded and survival was calculated. Effects of prognostic factors were compared. RESULTS: Sixty two patients were identified (36M, 26F; age 22‑84, median 51.5 years) and majorities (57%) of thymoma were stage I‑II. WHO pathological subtype B was most common 30 (49%). Mean tumor size was smaller in patients with myasthenia (5.3cm) than the entire group (7.6cm). Neoadjuvant therapy was offered to five unresectable stages III or IV a patient’s with 40% resectability rates. Median overall survival was 60 months (Inter quartile‑range 3‑44 months) with overall survival rate (OS) at three year being 90%. Resectable tumors had better outcomes (94%) than non resectable (81%) at three years. Mosaoka Stage was the only significant (P = 0.03) prognostic factor on multivariate analysis. CONCLUSION: This is first thymoma series from India with large number of patients where staging is an important prognostic factor and surgery is the mainstay of therapy. In Indian context aggressive multimodality treatment should be offered to advanced stage patients and which yields good survival rates and comparable.

Delay in seeking specialized care for oral cancers: Experience from a tertiary cancer center.

OBJECTIVE: Advanced oral cancers are a challenge for treatment, as they require complex procedures for excision and reconstruction. Despite being occurring at a visible site and can be detected easily, many patients present in advanced stages with large tumors. Timely intervention is important in improving survival and quality of life in these patients. The aim of the present study was to find out the causes of delay in seeking specialist care in advanced oral cancer patients. MATERIALS AND METHODS: A prospective questionnaire based study was done on 201 consecutive advanced oral squamous cancer patients who underwent surgery at our hospital. All patients had either cancer of gingivobuccal complex (GBC) or tongue and had tumors of size more than 4 cm (T3/T4) and were treatment naïve at presentation. RESULTS: Even though most patients observed abnormal lesions in their mouth, majority delayed the decision to visit a physician early. A significant percentage of patients (50%) also reported a delayed diagnosis by the primary care physician before being referred to a tertiary care center for definitive treatment. The average total duration from symptoms to treatment was 7 months. CONCLUSION: The main reasons of this delay in receiving treatment were due to patients themselves (primary delay) or due to time taken by the primary physician to diagnose the condition (secondary delay). Oral self-examination can be helpful in detecting oral cancers early.

Stereotactic body radiotherapy in early stage non-small cell lung cancer: First experience from an Indian Centre.

BACKGROUND: Surgery is the standard of care for early stage (T1-2, N0, M0) non-small cell lung cancer. A considerable number of these patients are ineligible for surgery due to age and comorbidities. Hypo fractionated high-dose stereotactic body radiotherapy (SBRT) is being performed for these group of patients. There is paucity of literature regarding this novel technique from the Indian subcontinent. AIMS AND OBJECTIVES: We hereby report the dosimetry, response and outcome of our small cohort of early stage non-small cell lung cancer patients treated with SBRT. MATERIALS AND METHODS: Between December 2007 and December 2010, 8 patients of early stage (T1-2N0M0) underwent SBRT at our centre. All the patients had undergone whole body PET-CT scan, MRI brain and pulmonary function test (PFT with DLCO). The SBRT schedules included 48 Gy in 6 fractions for peripherally located and 48 Gy in 8 fractions for centrally located tumors. Response and toxicity were assessed in 3 monthly follow up visits. RESULTS: The median duration of follow up was 18 months (range 8-44 months). The median age of the patients was 70 years (range 63-82 years) and the median tumor diameter was 4 cm (range 2.8-5.0 cm). The mean PTV volume was 165 cc(range 127.3- 193.9 cc). The mean dose to the PTV was 99.5% (range 97.7- 102.1%). After 3 months, 7 patients had complete metabolic response and 1 patient had partial metabolic response. Overall survival at 1.5 years was 87.5%. One patient had grade 2 pneumonitis. No toxicities of grade 3 or higher were identified. CONCLUSION: SBRT for early stage NSCLC resulted in excellent local control with minimal toxicity and can be considered as a treatment option in properly selected patients.

Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma.

Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 weekly regimen with cisplatin and docetaxel as 75 mg/m 2 each, 5-FU as 1000 mg/m 2 . NACT was either given with the intent of achieving: (1) surgical resection (extensive soft tissue disease, oropharyngeal involvement, extensive disease with cartilage erosion) or (2) organ preservation (Bulky disease with inner cartilage erosion, exolaryngeal disease without cartilage erosion, large N3 nodes). Results: The mean age of this population was 55 years. Most (83%) of the patients had pyriform sinus (PFS) involvement. 69% patients had Stage IVa disease, 21% Stage IVb and 10% Stage III. The overall response rate was 66%, including 06% complete responses and 60% partial responses. Following NACT, resectability was achieved in 30% (10/33) and organ preservation protocol was planned after NACT in 73% (19/26) patients. The main toxicities were neutropenia (grade 3, 4, 04%; febrile neutropenia, 4%), mucositis 5%, diarrhea 5%. The median progression free survival was 20 months. Conclusions: NACT can be useful in patients with oropharyngeal involvement to achieve surgical resection and larynx preservation in patients with bulky T3 disease.

Epidemiology of lung cancer in India: Focus on the differences between non-smokers and smokers: A single-centre experience.

Context: Lung cancer has varied epidemiology depending on the geographic region. Globally, there have been important changes in incidence trends amongst men and women, histology, and incidence in non-smokers. Indian epidemiological data on lung cancer is scarce. Aims: We set out to study the epidemiological patterns and clinical profile of lung cancer in India. Materials and Methods: We interviewed patients discussed in the thoracic oncology multidisciplinary meetings between 2008 and 2009. Demographic data, smoking history, place of residence, histology, stage at presentation, and treatment details were collected. Data was entered and analyzed in SPSS. Results: There were 489 patients, with a median age of 56 years, of which 255 (52%) were non-smokers and 234 (48%) were smokers. One hundred and thirty-three patients had consumed smokeless tobacco. The male-to-female ratio was 3.5:1. Sixty-nine patients (14.1%) were incorrectly diagnosed and treated with anti-tuberculosis treatment, which delayed the diagnosis of lung cancer by four months. Eight percent of patients had small-cell carcinoma; of the 92% patients with non-small-cell carcinoma (NSCLC), the most common histology was adenocarcinoma (43.8%), followed by squamous cell (26.2%), large cell (2.1%) and other (8.3%). Eighteen percent of patients were diagnosed by cytology, therefore were diagnosed as NSCLC, without further histologic subtyping. Most patients (43%) were in Stage III at presentation. Lung followed by bone were the common sites of metastases. The majority of the patients (49%) received palliative chemotherapy. Among definitive therapy, concurrent chemo-radiation (13%) was offered more frequently than surgery (6%). Conclusion: Considerably higher numbers of Indian patients with lung cancer are non-smokers, compared to the West. The global trend of rise in adenocarcinoma is paralleled in India. Non-tobacco-related risk factors need further investigation.

Cetuximab with radiotherapy in patients with loco-regionally advanced squamous cell carcinoma of head and neck unsuitable or ineligible for concurrent platinum-based chemo-radiotherapy: Ready for routine clinical practice.

Purpose : To report outcomes of cetuximab concurrent with radiotherapy in advanced head-neck cancer unsuitable for platinum-based chemo-radiotherapy. Materials and Methods : Retrospective chart review of 37 patients treated with cetuximab and radiotherapy at a comprehensive cancer centre. Results : Median age of study cohort was 59 years. Thirty four (92%) patients had advanced stage disease (stage III-IV). Reasons for ineligibility for platinum included impaired creatinine-clearance, old age, and/or co-morbidities. Thirty-two (86%) patients completed planned radiotherapy without interruption; 29 (80%) patients received ≥6 cycles of cetuximab. Fifteen patients (40.5%) developed ≥grade 3 dermatitis; 9 patients (25%) experienced ≥grade 3 mucositis. At a median follow-up of 16 months, the 2-year loco-regional control, disease-free survival, and overall survival was 35.5%, 29.5%, and 44.4% respectively. Stage grouping and severe dermatitis were significant predictors of outcome. Conclusions : Cetuximab concurrent with radiotherapy is a reasonable alternative in advanced head-neck cancer patients with acceptable compliance and outcomes, but higher skin toxicity.