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.

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.

Predicting outcome of advanced head-and-neck cancer by measuring tumor blood perfusion in patients receiving neoadjuvant chemotherapy.

PURPOSE: The purpose of this study was to correlate treatment response with tumor blood perfusion in patient of advanced head-and-neck cancer undergoing neoadjuvant chemotherapy. MATERIALS AND METHODS: A total of 40 patients of advanced head-and-neck cancer, who were planned for neoadjuvant chemotherapy, were included in the study. All patients underwent diagnostic computed tomography (CT) with perfusion study for staging and quantitative measurement of tumor volume as well as perfusion parameters (including tumor blood volume, blood flow, permeability, and time to peak enhancement), at baseline and after completion of neoadjuvant chemotherapy. Total 3 cycles of neoadjuvant chemotherapy with paclitaxel, cisplatin, and 5 fluorouracil were given. Tumor response was evaluated in terms of change in tumor volume and correlated with perfusion parameters. RESULTS: Out of 40 patients, 22 patients had more than 50% reduction in tumor volume, who were grouped as responder and remaining 18 patients had <50% decrease in tumor volume, grouped as nonresponder. Both the groups were similar in terms of age, gender, performance status, stage, nodal status, or addiction. Baseline CT scan shows a significant difference in tumor blood flow (P = 0.048) and marginal difference in time to peak enhancement (P = 0.058) in two groups. However, there is no difference in tumor blood volume (P = 0.32) and permeability surface area (P = 0.07). CONCLUSIONS: Evaluation of tumor blood flow by perfusion CT is helpful in predicting chemotherapy outcome and deciding appropriate treatment modality, but further evaluation with more number of patients is required for validating the predictive role of each perfusion parameters.

Rosai-Dorfman Disease of Right Atrium Mimicking Myxoma.

Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, is a rare multisystemic disorder that was first reported by Rosai and Dorfman in 1969. It is a distinct histioproliferative disorder due to overproduction of histiocytes, which accumulate in lymph nodes. The cardiac involvement of this disease is extremely rare, and until now, only 18 cases have been reported. We report the case of a 53-year-old woman with right atrial mass mimicking myxoma, which the histopathologic evaluation revealed to be Rosai-Dorfman disease of the right atrium.

The role of interstitial brachytherapy using template in locally advanced gynecological malignancies.

OBJECTIVE: Brachytherapy plays a major role in the treatment of patients with carcinoma of the cervix. However, routine intracavitary brachytherapy may not be feasible or adequate to treat locally advanced disease. The purpose of this prospective study was to assess treatment outcome for patients with locally advanced gynecological malignancies treated with interstitial brachytherapy using Martinez Universal Perineal Interstitial Template (MUPIT) and to study the acute and late sequelae after treatment by this technique. METHODS: Thirty previously untreated patients with histologically confirmed carcinoma of the cervix (20 patients), vault (7 patients), and vagina (3 patients) were treated by a combination of external beam radiotherapy using megavoltage irradiation to the pelvis to a dose of 4000 to 5000 cGy followed by interstitial brachytherapy using MUPIT between June 2000 to August 2001 at Gujarat Cancer and Research Institute, Ahmedabad. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitary radiotherapy was found to be unlikely to encompass the tumor volume were treated with interstitial template brachytherapy using MUPIT applicator and were enrolled for this study. Criteria for inclusion in this study were as follows: Hemoglobin--minimum 10 gm%; Performance Status--70% or more (Karnofsky Scale); Histopathological confirmation; FIGO Stage--IIb-IIIb (excluding frozen pelvis). RESULTS: Among the 30 patients studied, 4 lost to follow-up and they were excluded from the study. With a median follow up of 9 months, local control was achieved in (20/26) 76.92% patients. The local control was better for nonbulky tumors compared to bulky tumors irrespective of stage of disease. Local control rate was better in patients with good regression of disease after EBRT. The time gap between EBRT and implant also had an impact on the outcome. CONCLUSION: Interstitial template brachytherapy by MUPIT is a good alternative to deliver high-dose radiation in locally advanced gynecological malignancies where conventional brachytherapy application is either not feasible or unlikely to encompass tumor volume adequately. The locoregional control obtained is definitely better than external beam therapy alone and within the accepted range of complications. However, long-term follow-up is needed to comment on late morbidities.