Biodosimetric analysis of head and neck cancer patients undergoing radiotherapy by dicentric chromosome aberration assay.

BACKGROUND: Biodosimetry is the quantification of absorbed radiation dose using biological material obtained from an exposed individual. Radiation can cause different types of chromosomal aberrations, including stable aberrations like translocations and unstable ones like micronuclei, dicentric chromosomes (DC), acentric, and ring forms. Dicentric chromosome assay has become the "gold standard" for cytogenetic biodosimetry due to its reproducibility, specificity (low baseline rates), and sensitivity to low doses. Using existing calibration curves and models obtained from in vitro irradiation of blood, the yield of DCs can be used to estimate the average whole-body absorbed dose. PURPOSE: To evaluate and compare the in vivo dose-response relation of DC aberration formation in peripheral blood lymphocytes of head and neck cancer (HNC) patients undergoing radiotherapy (RT) alone, cisplatin-based chemoradiation (CCRT), accelerated fractionation RT (AFRT), and CCRT with gefitinib (GCRT). METHODOLOGY: This prospective observational and analytical study was conducted from 2018 to 2021 in the Department of Radiation Oncology and Genetic Lab of tertiary care, teaching hospital after approval from the Institutional Ethics Committee. Biodosimetric analysis was done weekly in patients undergoing RT (n = 20) versus CCRT (n = 20), CCRT (n = 12) versus AFRT (n = 12), and CCRT (n = 6) versus GCRT (n = 6). The yield of DCs was measured in blood samples taken before starting treatment, that is, day 0 and during RT on days 6, 11, and 16 in RT alone versus CCRT; on days 7 and 13 in CCRT versus AFRT; and days 6 and 11 in CCRT versus GCRT from a blood sample drawn 1-2 h after RT. Phytohemagglutinin-stimulated lymphocytes were cultured using heparinized blood in RPMI-1640 medium supplemented with fetal bovine serum. Cells were arrested at metaphase using demecolcine, harvested by centrifugation, mounted, and stained with Giemsa. Cytogenetic analysis was performed by analyzing at least 100 metaphases with well-spread chromosomes. DC aberrations and acentric fragments were identified and recorded. To standardize the findings as per the customized field for every patient, the mean DC yield per cm2 of the irradiated area was calculated and compared. RESULTS: The mean yield of DC/cm2 in the CCRT group was greater than the RT alone group by 16.33%, 28.57%, and 18.68% on days 6, 11, and 16 of treatment, respectively. This difference between the two groups at day 6 (P = 0.001), day 11 (P < 0.001), and day 16 (P < 0.001) was found to be statistically significant. The mean yield of DC/cm2 in the CCRT group was greater than the AFRT group by 7.9% and 18.3% on days 7 and 13 of treatment, respectively. This difference at day 7 (P < 0.001) and day 13 (P < 0.001) was found to be statistically significant. The mean yield of DC/cm2 in the CCRT group was greater than the GCRT group by 22.7% and 21.8% on days 6 and 11 of treatment, respectively. The difference at day 6 (P = 0.01) was statistically significant but, on day 11 (P = 0.065) this difference was found insignificant. CONCLUSION: There is a dose-dependent increase in the yield of DCs in lymphocytes of HNC patients undergoing RT with subsequent fractions. Cisplatin-based chemoradiation is the superior method of treatment intensification radio-biologically proven by higher DC yield.

Extracorporeal irradiation in malignant bone tumors: Single institution experience and review of literature.

In the last couple of decades, the management of malignant bone tumor (MBT) has seen a sea change. With the advent in surgical technics, radiation therapy, and chemotherapy, it has moved from disabling amputation to limb salvage surgery. Extracorporeal irradiation (ECI) and re-implantation of resected bone is a useful method of limb salvage of MBTs. In our study, we analyzed and presented the results of 8 cases of MBTs treated with this modality. Between 2014 and 2017, 8 patients with primary MBT were enrolled for ECI technique who are meeting the eligibility criteria. Before taking the patient for ECI treatment, a multispecialty tumor board discussion was done for each patient. All of them received neo-adjuvant and adjuvant chemotherapy except the patients with histology of giant cell tumor. Following neoadjuvant chemotherapy bone excision surgery was performed, and the resected bone was taken for ECI with the dose of 50 Gray in a single fraction. After ECI, bone segment was re-implanted at osteotomy site in the same setting. After completion of adjuvant chemotherapy, the patients were then followed up for any sequelae, local and systemic control, ambulation, and functional outcome. Out of 8 patients, there were 5 males and 3 females with mean age of 22 (range 13-36). The involved bone was the tibia in 6 patients, ischium in 1 patient, and femur in 1 patient. Histopathologically, the malignancies included 3 osteosarcoma, 3 Giant cell tumor, 1 Ewing's sarcoma and 1 chondrosarcoma. At median follow-up of 12 months (range 6-26 months), local control rate was 87.5% and systemic control rate was 75%. Perioperative ECI and re-implantation is a useful, convenient, and inexpensive technique. The overall treatment time is reduced. The patient's own bone fits perfectly to the resection site with reduced risk of graft site infection. The risk of local recurrence due to tumor re-implantation is negligible with tumoricidal radiation doses of ECI, and it is usually associated with manageable sequelae. Recurrence rates are acceptable and salvageable with surgery.

Feasibility of preirradiation temozolomide in cases of high-grade gliomas: Our experience and review of literature.

Aim: The purpose of this study was to evaluate the efficacy and safety of preradiation temozolomide (TMZ) in high-grade gliomas. Study and Design: It is a single-center, single arm, prospective study. The study included postoperative, histopatholgically proven cases of high-grade gliomas. Materials and Methods: Nine patients of anaplastic astrocytoma (AA) and twenty patients of glioblastoma multiforme (GBM) were enrolled in the study. All patients had undergone partial or complete resection. Three weeks after surgery, patients were started on chemotherapy, consisting of two cycles of TMZ, 150 mg/m2/day for 5 days, repeated at an interval of 4 weeks. Patients were subsequently treated with concomitant chemoradiotherapy. A dose of 60 Gy was given over thirty fractions along with TMZ, 75 mg/m2/day. Four cycles of TMZ were given after completion of radiotherapy, in a dose and manner similar to preradiotherapy. Statistical Analysis and Result: Treatment-related toxicity was assessed using common terminology for toxicity criteria (CTCAE v4). Progression-free survival and overall survival (OS) analysis was done. Nearly 79% of patients completed the two cycles of preradiation chemotherapy. Chemotherapy was tolerated well. Median time to progression was 11 months and 8.2 months in AA and GBM patients, respectively. Median OS was 17.4 months in AA patients and 11.4 months in GBM patients. Conclusions: Most patients of postoperative high-grade gliomas tolerated two cycles of TMZ. A good safety profile of TMZ allows it to be used in frontline settings, especially in high volume centers where a delay in starting radiotherapy frequently occurs. The use of TMZ before radiotherapy is a safe and feasible approach, and further studies are required to validate this approach.

Epidemiological characteristics of endometrial cancer patients treated at a tertiary health center in National Capital Territory of India.

Settings and Design: A retrospective study which analyzed the data of female patients attending a tertiary care center in National Capital Territory for the treatment of endometrial cancer. Materials and Methods: Eighty-six histopathologically confirmed cases of carcinoma endometrium were taken from January 2016 to December 2019. Detailed information was collected regarding patient's case history, sociodemographic data (age of presentation, occupation, religion, residence, and substance addiction), clinical presentation, diagnostic and therapeutic procedures, and known risk factors (age at menarche and menopause, parity, obesity, use of oral contraceptive pills, hormone replacement therapy, and comorbidities such as hypertension and diabetes). Statistical Analysis Used: After analysis, results were presented as mean ± standard deviation and frequency. Results: Eighty-six percent of the patients (n = 73) were in the age group of 40-70 years; the mean age of the patients at diagnosis of endometrial cancer was 54 years. Eighty-one percent (n = 70) of the patients were from urban areas. Sixty-seven percent of the females (n = 54) were Hindu. All the patients were housewives with nonsedentary lifestyles. Most patients (88%; n = 76) presented with bleeding per vaginum. Fifty-nine percent (n = 51) had stage I disease, followed by 15% (n = 13) with stage II, 14% (n = 12) with stage III, and 12% (n = 10) with stage IV disease. Eighty-two percent (n = 72) of the patients had endometrioid carcinoma. Other less common variants were mixed Mullerian malignant tumor, squamous, adenosquamous, serous, and endometrioid stromal. Forty-four percent (n = 38), 39% (n = 34), and 16% (n = 14) of the patients had grade I, grade II, and grade III tumor, respectively. 53.5% of the cases (n = 46) had >50% myometrial invasion at the time of presentation. Eighty-two percent (n = 71) of the patients were postmenopausal. The mean age at menarche and menopause was 13 years and 47 years, respectively. Fifteen percent (n = 13) of the females were nulliparous. Forty-six percent (n = 40) of the patients were overweight. Most patients (82%) had no history of addiction. Twenty-five percent (n = 22) of the patients had hypertension, and 27% (n = 23) has diabetes as comorbidity. Conclusions: The incidence of endometrium cancer is showing a steady rise in the recent past. Early age of menarche, late age of menopause, nulliparity, obesity, and diabetes mellitus are well-documented risk factors for uterine cancer. Better outcome and control of disease is possible by understanding of endometrial cancer etiology, risk factors, and its preventive measures. Thus, a robust screening program is warranted to detect the disease in early stage and for increased survival.

Microsatellite instability in colon cancer: A single center experience from North India.

Background: Due to the defects of mismatch repair (MMR) genes MLH1, PMS2, MSH2, and MSH6, the mutations which occur in microsatellite region are not repaired during deoxyribonucleic acid synthesis, leading to microsatellite instability (MSI). MSI is one of the major molecular changes that occur in colorectal carcinoma (CRC). Studies have shown that MMR deficient CRC has different clinicopathological characteristics and a better stage adjusted survival when compared to microsatellite stable tumors. Materials and Methods: We have retrospectively analyzed the cases of colon cancers treated in our institute for 3 years from 2017 to 2019. Most of the patients underwent surgery and received adjuvant chemotherapy. MSI testing was done in surgical specimen with immunohistochemistry. The clinical details of the patients were tabulated in Microsoft Excel, and statistical analysis was done using IBM SPSS Statistics for Windows, version 21 (IBM Corp., Armonk, NY, USA). Results: A total of 52 patients who were treated in our institution from 2017 to 2019 were analyzed. The mean age was 46.8 ± 13.5 (19-72) years. The male-to-female ratio was 8:5. No significant association in patient demographics and clinicopathological parameters was observed between MSI stable and unstable disease. However, lymphovascular invasion showed a significantly higher trend in MSI unstable patients (P = 0.052). The median progression-free survival (PFS) of the entire cohort was 27.8 months (95% confidence interval = 22.7-32.9) and the median overall survival (OS) is not reached. The median PFS is 21.3 months in MSI stable patients whereas it is not reached in MSI unstable patients (P = 0.049). The median OS is 27.1 months in MSI stable patients, but it is not reached in MSI unstable patients and the difference shows a trend towards statistical significance (P = 0.061). Conclusion: MSI unstable tumors were found to have higher PFS and higher OS in our study. It needs prospective validation in larger studies in Indian scenario.

Highly aggressive gastric adenocarcinoma with multiple skin nodule and supraclavicular node in a 19-year-old patient: A rare presentation in such young age.

Although gastric adenocarcinoma is common in middle- and old-aged population, it is rare in young people. Development of cutaneous metastasis during presentation is even rarer in any age group. We report the case of a 19-year young man with gastric adenocarcinoma who had multiple skin nodules over the trunk during presentation. Fine-needle aspiration cytology of the nodule revealed it to be metastasis from gastric adenocarcinoma. Cutaneous metastasis may be the first presentation of internal malignancies even with a short history of disease in young patients. Atypical presentation of a malignancy in atypical age group must be evaluated with prompt assessment, active intervention, and close follow-up.

Complete androgen insensitivity syndrome with intra-abdominal seminoma in a phenotypic female: A rare presentation.

Androgen insensitivity syndrome (AIS) is a rare, X-linked recessive disorder which causes alterations in androgen receptor gene leading to hormone resistance, which may present clinically under three phenotypes: complete AIS (CAIS), partial AIS, or mild AIS. The symptoms range from phenotypically normal males with impaired spermatogenesis to phenotypically normal women with primary amenorrhea. We report a case of a 35-year-old woman who was diagnosed with CAIS and presented with malignant transformation of the undescended testis. The histopathology confirmed the presence of seminoma. In this case report, we reviewed the literature which describes the biochemical and endocrinological abnormalities leading to the syndrome. It also highlights the potential for malignant changes of the undescended testes, diagnosis, and therapeutic management.

Demographic and clinicopathological profile of patients of gastrointestinal stromal tumor from a tertiary care center of North India: An observational study.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal system. This study was aimed to analyze the demographic and clinicopathological data of the patient with a primary diagnosis of GIST, who were treated at our center. MATERIALS AND METHODOLOGY: Patients of GIST registered at our center from September 1, 2008, to August 31, 2016, were enrolled for this study. Patient's demographic and clinicopathological data were collected from clinical records. The data were represented as absolute number, percentage, and median (range: minimum to maximum), whichever applicable. RESULTS AND OBSERVATIONS: The analysis of 27 patients revealed that pain was the most common clinical feature. The stomach was the most common primary site. Most of the patients underwent upfront radical surgery (92.6%) followed by adjuvant imatinib. Histopathological data revealed that most tumors were >10 cm in size, 51.8% of patients had low mitotic index, and all these patients were either immunohistochemical positive for cluster differentiation 117 or KIT. The median duration of tyrosine kinase inhibitors therapy (imatinib) in our study individual was 2.5 years with a range of 4.8 months-3 years. Response assessment revealed 74.1% complete remission, 11.1% stable disease, and 3.7% progressive disease. Median overall survival in study individuals was 2.63 years (range: 0.1-8.6 years). Patient- and tumor-related factors were analyzed for prognostic significance using univariate survival analysis; however, none was found to have a significant prognostic correlation. CONCLUSIONS: Patients who underwent upfront surgery followed by adjuvant imatinib has shown good response to the treatment. However, the limitation of the small sample size and short follow-up in this study may not be a true data representation of the entire population.

Changing pattern of fungal infection in burn patients.

Invasive fungal burn wound infection is an important emerging cause of late onset morbidity and high mortality in patients with major burns. Following a pilot study done in our unit in 1 year, i.e. January 2008-March 2009 in 71 patients where 28% (20 patients) of the burn wound biopsies from suspected cases showed fungal wound invasion (FWI), a detailed study was planned in order to study the epidemiology of fungal infection in burns in our unit wherein routine wound biopsies in 100 patients were sent on 7th, 14th and 21st postburn day over a one year period (July 2009-June 2010). 12 patients (12%) were diagnosed with FWI on culture. This was then followed by another study in a 9 month period (July 2010-March 2011) when wound samples for only 36 patients in whom there was clinical suspicion of fungal infection were sent. 16 of these patients were diagnosed with fungal wound invasion (FWI) thus establishing an incidence of 44% from suspected cases. These studies showing the increase in fungal infection in our unit have therefore made us wiser, increased our awareness and our accuracy in diagnosing this uncommon infection in extensive burns where patient is not only severely immunocompromised but also has many other risk factors making them more vulnerable to fungal invasion. Another glaring fact which emerged from these studies was the rising incidence of nonalbicans Candida infection compared to Candida albicans, especially C. tropicalis and C. krusei which are more severe in nature and associated with a higher mortality. This signifies that there is a shift of FWI in burns from commensal organism, i.e. C. albicans to pathogenic nosocomial organisms, i.e. C. nonalbicans.