Dinesh Chandra Doval

Efficacy and safety of granulocyte macrophage-colony stimulating factor (GM-CSF) on the frequency and severity of radiation mucositis in patients with head and neck carcinoma

PURPOSE Based on the clinical evidence of mucosal protection by GM-CSF during cytotoxic chemotherapy, a pilot study was undertaken to determine the safety and mucosal reaction of patients receiving GM-CSF while undergoing definitive conventional fractionated radiotherapy in head and neck carcinoma. METHODS AND MATERIALS Patients were considered eligible if buccal mucosa and oropharynx were included in the teleradiation field. Ten adult patients with squamous cell carcinoma of head and neck (buccal mucosa--8 and posterior 1/3 tongue--2) were entered into the trial. Radiation therapy was delivered with telecobalt machine at conventional 2 Gy fraction and 5 fractions/week. The radiation portals consisted of two parallel opposing lateral fields. GM-CSF was given subcutaneously at a dose of 1 microg/kg body weight, daily, after 20 Gy until the completion of radiation therapy. Patients were evaluated daily for mucosal reaction, pain, and functional impairment. RESULTS The median radiation dose was 66 Gy. Eight patients received > or = 60 Gy. The tolerance to GM-CSF was good. All 10 patients completed the planned daily dose of GM-CSF without interruption. Mucosal toxicity was Grade I in four patients till the completion of radiotherapy (dose range 50-66 Gy). Six patients developed Grade II reaction, fibrinous mucosal lesions of maximum size 1.0-1.5 cm, during radiotherapy. None developed Grade III mucositis. The maximum mucosal pain was Grade I during GM-CSF therapy. In two patients after starting GM-CSF the pain reduced in intensity. Functional impairment was mild to moderate. All patients were able to maintain adequate oral intake during the treatment period. Total regression of mucosal reaction occured within 8 days following completion of radiotherapy. CONCLUSIONS GM-CSF administration concurrently with conventional fractionated radiotherapy was feasible without significant toxicity. The acute side effects of radiotherapy namely mucositis, pain, and functional impairment were nil to minimal. The results are suggestive of mucosal protection by GM-CSF during radiotherapy and warrants further study in randomized double blind trial.

Rhabdomyosarcoma of the tongue

Although rhabdomyosarcoma (RMS) has a predilection for the head and neck region its occurrence in the tongue is uncommon. We report 2 cases of RMS of the tongue, 1 paediatric and 1 adult patient. The child who had RMS of the alveolar type involving anterior two-thirds of the tongue was treated with surgery and chemotherapy and is disease-free at 84 months of follow-up. The adult patient had locally extensive embryonal RMS of posterior third of the tongue, received chemotherapy and radiotherapy but died with progressive disease at 24 months of follow-up.

Gastric cancer in India

As per the 2001 census, the population of India is 1027015 247. The burden of new cancer cases has been estimated based on data from five population-based cancer registries (Bangalore, Barshi, Bhopal, Chennai, and Delhi) in the network of the National Cancer Registry Programme in India. The estimated number of new cancer cases in 1995 was 311460 in men and 340 683 in women [2]. Lung cancer is the most common cancer among males, with cervical cancer the most common in females. Crude incidence rates (CRs) and age-adjusted incidence rates (AARs) per 100000 (1990–1996) for all sites are shown in Table 1. The CR was lowest in Barshi and highest in Chennai for both males and females. The AAR was highest in Delhi for both males and females [3]. The crude mortality rate was highest in Chennai, whereas the age-adjusted mortality rate was highest in Mumbai for both males and females (Table 2) [3]. Tobacco-related cancers constitute 32.7% of total cancers seen in India. The number of new digestive tract cancer cases in 2001 was estimated to be approximately 145000 in India. In men and women, the esophagus (24925 in men and 18608 in women) is the commonest site, followed by the stomach (n 23785 in men; 11 890 in women) [4]. The AAR of gastric cancer in urban registries (3.0– 13.2) is on the lower side among those reported worldwide (4.1–95.5). It is a disease mainly of males. Gastric cancer occurs a decade earlier among South Indians compared with the North Indians [5].

Isolated hypoglossal nerve palsy due to skull base metastasis from breast cancer

We describe a 44-year-old woman who presented with an isolated unilateral hypoglossal nerve paralysis caused by a skull base metastasis from breast cancer. The patient had a modified radical mastectomy followed by local radiotherapy and adjuvant chemotherapy. Fourteen months later she presented with difficulty in speaking. Physical examination revealed an isolated left hypoglossal nerve paralysis. The MRI scan showed a mass lesion involving the left occipital condyle extending into hypoglossal canal.

A retrospective study of patients with locally advanced cancer of the cervix treated with neoadjuvant chemotherapy followed by radical surgery.

New concept of downstaging locally advanced cancer of the cervix (LACC) with neoadjuvant chemotherapy (NACT), to make it resectable, is of great interest and needs to be explored. This is a retrospective study of 56 LACC patients. Efficacy of NACT was measured in terms of optimal pathological response (OR). Percentage of patients who needed adjuvant radiotherapy and disease-free interval at 2 years was evaluated. Clinically, 49 patients (87.5%) responded well to NACT with TIP regimen (paclitaxel, ifosfamide, and cisplatin) and underwent radical surgery. Adjuvant radiation was given for adverse factors in histopathology. Recurrences were noted; 46.4% of patients were in stage 2b, followed by 25% in stage IIIb; 92.8% of patients had squamous cell carcinoma. Optimal pathological response was seen in 15 patients (30.6%) with complete response in 8 patients (16.3%). Four patients (8.2%) had deposits in the parametrium, and 11 (22.4%) had positive nodes. On gross examination, 48.9% of patients had complete disappearance of cervical growth, and there was no microscopic evidence of cervical malignancy in 16.3%. In 20.4% of patients, cervical cancer was reduced to cervical intraepithelial neoplasia or microinvasion. Thirty-four patients (69.4%) needed full adjuvant radiotherapy. Overall, 14 patients (25.92%) had recurrence, with 11 (22.44%) being in NACT and radical surgery group. At 2 years, disease-free interval for 49 patients who underwent radical surgery was 69%. This study suggests that LACC patients who respond to NACT are surgically resectable with pathological cure in some cases, who are then spared from adjuvant radiation, which is given when recurrence occurs. However, with advancing stage, the percentage of OR decreases, and the need of adjuvant radiation increases.

Report of a Case of Pericardial Mesothelioma with Liver Metastases Responding Well to Pemetrexed and Platinum-Based Chemotherapy

Pericardial mesothelioma remains a disease with a bleak prognosis. We report the case of a patient with metastases to liver and good response to pemetrexed and carboplatin-based combination chemotherapy and consequent prolonged progression-free survival.

Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A single center study

Background: Adenocarcinoma, a subgroup of non-small cell lung cancer, is the most frequent form occurring in the non-smokers. Mutation in tyrosine kinase domain of epidermal growth factor receptor (EGFR) has been a common feature observed in lung adenocarcinoma. The study was carried out to detect the prevalence of EGFR mutation in lung adenocarcinoma. Materials and Methods: EGFR mutation status in 166 lung adenocarcinoma patients was obtained retrospectively. Mutation tests were performed on paraffin embedded tissue blocks as a routine diagnostic procedure by polymerase chain reaction followed by direct nucleotide sequencing. Patient’s demographics and other clinical details were obtained from the medical records. Results: EGFR mutation was detected in 43/166 (25.9%) patients. Gender wise mutation was observed as 18/55 (32.7%) in females and 25/111 (22.5%) in males. Overall, EGFR mutation was correlated with never smokers and distant metastasis (P < 0.05), but not associated with the gender, disease stage and pleural effusion. Exon 19 deletions were significantly correlated with females, never smokers, pleural effusion and distant metastasis (P < 0.05). However, point mutation on exon 21 did not show any statistical association with the above variables. Median overall survival was 22 months (95% confidence interval, 15.4-28.6). Female sex, EGFR mutation and absence of metastasis are associated with good prognosis. Conclusion: EGFR mutation in lung adenocarcinoma was higher in never smokers, females and patients with distant metastasis. However, it was not linked with tobacco smoking. The prevalence of EGFR mutation observed is in range with the previously published reports from the Asian countries.

Expression of epidermal growth factor receptor, p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma

Background: The present study observed the expression levels of epidermal growth factor receptor (EGFR), p53, Bcl2, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (cox-2), cyclin D1, human epidermal receptor-2 (HER-2) and Ki-67 in gallbladder carcinoma (GBC) and their association with clinicopathological profiles and disease outcomes. Materials and Methods: Fifty consecutive samples of cholecystectomy/biopsies from GB bed (archived formalin fixed paraffin embedded tissue blocks of different stages of GBC) were included, and patient details related to their demographic profile, investigations, tumor profile, treatment, and follow-up were recorded. Immunohistochemistry was performed to study the expression levels. Results: Overexpression of EGFR, p53, Bcl2, VEGF, cox-2, cyclin D1 and HER-2 was observed as 74%, 44%, 8%, 34%, 66%, 64%, and 4%, respectively. Association of Bcl2 overexpression in mucinous morphology (40%, P = 0.045), cox-2 overexpression in early stage (I/II) tumors (87.5%, P = 0.028) and VEGF overexpression in alive patients (47.1%, P = 0.044) was observed. Co-expression of EGFR and p53 were statistically significant (P = 0.033). Ki-67 labeling index was significantly higher in patients in age group <40 years (P = 0.027), and poorly differentiated tumors (P = 0.023). Advanced disease and poorly differentiated tumors showed a significantly poor median survival (P < 0.05). Conclusion: EGFR, cox-2 and cyclin D1 were largely overexpressed. Advanced tumor stages and poorly differentiated tumors are predictors of poor survival.

Immunohistochemical Profile of Breast Cancer Patients at a Tertiary Care Hospital in New Delhi, India

BACKGROUND To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. MATERIALS AND METHODS This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. RESULTS A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value<0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). CONCLUSIONS The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.

Primary testicular non-Hodgkin's lymphoma: a review article

O linfoma primario do testiculo (LPT) foi descrito como uma entidade clinica pela primeira vez em 1866. E uma doenca rara e corresponde a 1% de todos os linfomas nao-Hodgkin, 2% de todos os linfomas extranodais e 5% de todos as neoplasias testiculares. E o tumor testicular mais comum em homens entre 60 e 80 anos de idade. LPT e unico em sua elevada incidencia de envolvimento bilateral (8-38%), sendo o tumor testicular bilateral mais comum. Tem uma predilecao por disseminacao para regioes extranodais nao-contiguas, especialmente para o sistema nervoso central (SNC). Estagios avancados da doenca sao usualmente tratados com quimioterapia a base de doxorubicina. Para os estagios mais precoces, as opinioes sao divergentes quanto a quimioterapia associada a orquiectomia. A alta prevalencia de disseminacao, especialmente para o SNC, sugere o uso de quimioterapia intratecal como profilaxia. Estudos prospectivos multicentricos incluindo um grande numero de pacientes poderiam resolver a questao com relacao ao manejo deste subtipo de linfoma nao-Hodgkin.Primary testicular non-Hodgkins lymphoma was first described as a clinical entity in 1866. It is a rare disease and accounts for 1% of all non-Hodgkins lymphoma, 2% of all extranodal lymphomas and 5% of all testicular neoplasms. It is the most common testicular tumor in males between sixty and eighty years of age. Testicular non-Hodgkins lymphoma is unique in its high incidence of bilateral involvement (8-38%), and it is also the most common bilateral testicular tumor. Testicular non-Hodgkins lymphoma has a predilection for spreading to non-contiguous extranodal sites, especially the central nervous system. Advanced-stage disease is usually managed with doxorubicin-based chemotherapy. For early-stage disease, opinion is divided regarding systemic chemotherapy following orchidectomy. The high incidence of spreading, especially to the central nervous system, leads to advocacy of the use of central nervous system prophylaxis with intrathecal chemotherapy. Prospective multicenter trials incorporating a large number of patients may lead to better guidelines for optimal management of this subtype of non-Hodgkins lymphoma.