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.

Leiomyosarcoma of sphenoid sinus- A rare tumor at an unusual site.

Leimyosarcoma (lms) is a malignant soft tissue tumor of smooth muscles. The tumor arises intramuscularly and in subcutaneous locations. It is unusual to encounter lms in head and neck region, even more infrequent to discover lms in nasal and paranasal sinuses. A case of 28 years old male with leiomyosarcoma originating from sphenoid sinus with intracranial extension is being presented with aim to highlight its rarity and to highlight the differential diagnosis and the need for prudent diagnosis in the work-up of the patient.

Epithelial myoepithelial carcinoma: A case report.

ABSTRACT: Epithelial myoepithelial carcinoma is a rare tumor with the parotid gland being the most common primary site of origin. The tumor may also very rarely originate in minor salivary glands of the soft palate. Due to the rarity of its occurrence and histogenesis, clear-cut therapeutic guidelines are not defined. The present report describes the case of a 56-year-old female patient who was diagnosed to have epithelial myoepithelial carcinoma (EMC) of the minor salivary gland of the soft palate, Stage T2 N0 M0 (Stage group II). The patient was treated with radical radiotherapy followed by adjuvant chemotherapy and is alive with no evidence of disease after 12 months following the end of treatment.

Pancreatic heterotropia in gallbladder with adenocarcinoma: A rare incidental finding.

ABSTRACT: Heterotopic pancreas is defined as the presence of aberrant pancreatic tissue present outside the pancreas without connection to its neural, vascular, and anatomic location. The commonly seen locations are stomach, duodenum, jejunum, Meckel commonly seen locatio, and ampulla of Vater. The gallbladder is an extremely rare site for pancreatic heterotropia. Its association with adenocarcinoma has not been described yet. A case of 50-year-old male with pancreatic heterotropia along with carcinoma gallbladder is being presented here.

Is postoperative radiotherapy (PORT) a viable option in high-risk early-stage cervical cancer after upfront or downstaged radical surgery? A comparative study.

BACKGROUND: Radical surgery for cervical cancer has inherent benefits, and as upfront or post neoadjuvant chemotherapy (NACT), is extendable to locally advanced cancer cervix (LACC), with postoperative radiotherapy (PORT) for high-risk factors. Objective of the study was to compare the effectiveness and survival between non-PORT and PORT in high-risk early stages. MATERIALS AND METHODS: Radical hysterectomies conducted between January 2014 and December 2017 were evaluated and followed till December 2019. Clinical, surgical-pathologic characteristics, and oncological outcomes were compared between non-PORT and PORT groups. A similar comparison was made between alive and dead patients within each group. The impact of PORT was assessed. RESULTS: Of 178 radical surgeries, early-LACC constituted 70%. Most (37%) of the patients belonged to stage 1b2, while stage 2b formed 5%. Mean age of patients was 46.5 years; 69% were below 50 years of age. Abnormal bleeding (41%) was the predominant symptom, followed by postcoital (20%) and postmenopausal bleeding (12%). Upfront surgeries formed 70.2%, and the average waiting period was 1.93 months (range: 1-10 months). PORT patients were 97 (54.5%) in number and the remaining formed the non-PORT group. Mean follow-up was 34 months, with 118 (66%) alive patients. Significant adverse prognostic factors were tumors >4 cm (44.4% patients), positive margins (10%), lymphatic vascular space invasion (LVSI; 42%), malignant nodes (33%), multiple metastatic nodes averaging seven (range: 3-11), and delayed (>6 months) presentation, but not deep stromal invasion (77% patients) and positive parametrium (8.4% patients). PORT overcame the adverse effects of tumors >4 cm, multiple metastatic nodes, positive margins, and LVSI. Total recurrences (25%) were balanced for both groups, but recurrences within 2 years were significantly more for PORT. Two-year overall survival (78%) and recurrence-free survival (72%), median overall survival (21 months), and median recurrence-free interval (19 months) were significantly better for PORT, with the complication rates being similar. CONCLUSION: PORT had significantly better oncological outcomes compared to non-PORT. Multimodal management is worthwhile.

Cutaneous metastasis in bladder cancer.

Cutaneous manifestation of cancers is a rare occurrence, even more so for bladder cancer, with a limited number of published reports. Iatrogenic implantation has been a major cause for it. With no clear distinction pattern from other common dermatological lesions, scattered occurrence, and poor survival; no definitive strategies are present for the management of these dermal manifestations. The present article describes a case of scalp lesion consistent with metastatic urothelial carcinoma along with a review of the literature.

Carcinosarcoma of buccal mucosa: A case report.

Carcinosarcoma is an extremely rare variant of squamous cell carcinoma characterized by biphasic histology defined by epithelial and mesenchymal components. Because of the aggressive nature, early risk of metastasis, and high mortality, this tumor is associated with poor prognosis. Surgery is considered as the main modality of treatment, although radiotherapy can be discussed in inoperable cases. The present paper describes a rare case of carcinosarcoma of buccal mucosa.

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.

Utility of Glasgow Microenvironment Score as a prognostic tool in colorectal carcinoma.

Background: Colorectal carcinoma (CRC) is third most common malignancy in the world. The presence of Lymphocytes particularly at the invasive margin of the tumor have been associated with good immune response indicating better prognosis. The relative tumor stroma is also important in deciding the course of the disease. The Glasgow Microenvironment Score (GMS) comprises of assessment of tumor cell infiltrate using Klintrup-Makinen (KM) grade and tumor stroma percentage. Aims: The aim of the present study is to evaluate the utility of GMS score in relation to parameters of adverse histopathological outcome in carcinoma colon that is grading, staging, LVI, PNI and nodal metastasis. Setting and Design: Colectomy specimens received over 3 year period were subjected to microscopic evaluation for LVI, PNI, grade, stage & lymph node metastasis. Materials and Methods: Lymphocytes at the deepest invasive margin of tumor were counted as per KM score in 5 HPF by two independent pathologists . Patients were classified as Low grade (0/1) or high grade (2/3) response. Tumor stroma percentage was calculated as stroma poor (<50%) and stroma rich (>/= 50 %). The GMS was scored by combining the two and scored 0, 1 and 2. Statistics and Results: Total 37 patients with no prior therapy were included out of which 23 were males and 14 females. 15 patients (40.54%) had GMS of 0, 6 (16.21%) had GMS 1 and 16 (43.24%) had GMS 2. A high GMS was associated with LVI (P = 0.02), PNI (P = 0.01) lymph node metastasis (P = 0.003). However, no significant association was found between GMS with Grade (P = 0.98) and Stage (P = 0.36). Conclusion: Low GMS was associated with good outcome and high GMS with poor outcome. This score can be used for risk stratification, can be of clinical utility and may be applied to pathological descriptions of CRC.

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.

Rituximab biosimilar for the treatment of diffuse large B-cell lymphoma: a phase 3 randomized study in India.

PURPOSE: Very few studies have demonstrated the rituximab biosimilarity in terms of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity in patients with diffuse large B-cell lymphoma (DLBCL) in India. Therefore, we compared the efficacy, safety, pharmacokinetic, pharmacodynamic, and immunogenicity of our biosimilar rituximab with the reference rituximab (Ristova, Roche products [India] Pvt. Ltd) in patients with DLBCL in India. METHODS: A phase 3, randomized, assessor-blind, parallel-group, two-arm study was conducted across 28 sites in India. A total of 153 newly diagnosed DLBCL patients were randomized to receive either biosimilar rituximab or reference rituximab. The study drugs were administered at a dose of 375 mg/m2 by intravenous infusion every 3 weeks for six cycles. The primary end point was objective response rate (ORR) at the end of Cycle 6. Secondary end points included: pharmacokinetic, pharmacodynamics, immunogenicity, and safety assessment. RESULTS: The ORR at the end of Cycle 6 was 82.14% in the biosimilar rituximab and 85.71% in the reference rituximab group. The risk difference (90% CIs) was - 3.57 (- 14.80, 7.66). It met the non-inferiority margin of - 20%. The pharmacokinetic and pharmacodynamic parameters were comparable between the two treatment groups. The incidence rate of immunogenicity was very low and similar in both the treatment groups. The safety profile of both the treatments was comparable with no major difference in terms of nature, frequency and severity of TEAEs. CONCLUSION: The study demonstrated the biosimilarity between the biosimilar rituximab and the reference rituximab. Our biosimilar rituximab could add to the cost-effective treatment alternatives for patients with DLBCL in India.

Osteosarcoma of the jaw: Primary versus secondary - A report of two cases.

ABSTRACT: Osteosarcoma (OS) is the most common primary malignancy of bone excluding hematological malignancies. Most common sites of tumor are long bones of extremities. OS of the jaw are extremely rare with mandible being more commonly after than maxilla. Hereby, we present two cases of OS of jaw with one patient being male and other female.

Primary neuroendocrine tumors of ovary: A clinicopathological spectrum in a tertiary care hospital with review of literature.

AIM: Primary neuroendocrine tumors in the ovary are rare. These tumors arise from the neuroendocrine cell system of ovarian stroma and surface epithelium, and may also arise from teratoma. We present four primary ovarian neuroendocrine tumors and discuss clinical, histomorphological, and immunohistochemical findings. METHODS: Four primary ovarian neuroendocrine tumors were identified from our 4-year departmental archives. H and E slides and immunostains were reviewed. Clinical history, imaging studies, and follow-up data were obtained from medical records. RESULTS: Patients' age ranged from 37 to 45 years. All the patients presented with abdominal discomfort, abnormal uterine bleeding, and unilateral or bilateral ovarian masses. Two of the cases were primary ovarian carcinoid tumors, one being the pure primary ovarian carcinoid tumor (PPOCT), and the other being associated with mature cystic teratoma, while the other two cases were neuroendocrine carcinoma. All the cases showed expression of neuroendocrine markers, namely, synaptophysin, chromogranin, and NSE. CONCLUSIONS: Primary neuroendocrine tumors in the ovary are rare and consist of a group of heterogeneous tumors that express similar immunohistochemical markers.

Transformation of diffuse large B-cell lymphoma to lymphoblastic lymphoma.

Transformations in diffuse large B-cell lymphoma (DLBCL) are extremely rare. Here, we are presenting a very rare case of DLBCL transforming into lymphoblastic lymphoma (LBL) diagnosed by fine-needle aspiration cytology (FNAC) and flow cytometry. A 31-year old male on antiretroviral therapy and a known case of diffuse large B-cell lymphoma diagnosed 1 year back on cervical lymphadenopathy, presented with left axillary swelling for 3 months. FNAC and Flow cytometry were performed from the left axillary swelling which confirmed the diagnosis of LBL.

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.

Expression of IL-6, TNF-α, and hs-CRP in the serum of patients undergoing single-sitting and multiple-sitting root canal treatment: A comparative study.

Background: In recent times, single-sitting root canal therapy has gained momentum over multiple-sitting root canal therapy due to its superior clinical outcome and less time required for treating the patient. Aim: Thus, the aim of current study was to compare the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in the serum of patients undergoing single-sitting and multiple-sitting root canal treatment. Materials and Methods: This cross-sectional experimental study was conducted on 300 subjects who were indicated for root canal treatment. Subjects were categorized into Group I (single visit) and Group II (multiple visits).Clinical data was obtained and serum samples were collected both before and after 1 week of treatment completion. Inclusion criteria were those patients (a) over 18 years of age, (b) without any disease of inflammatory etiology, and (c) who had not previously received endodontic treatment or any related therapeutic treatment. Exclusion criteria were those (a) without a complete clinical history, (b) with greater than one indicated tooth, (c) who did not complete their treatment, and (d) with any periodontal disease. Chi-square and Student's t-test were applied. Results: It was found that in single-sitting root canal treatment, there was a statistically significant reduction in these inflammatory biomarkers, although no difference in clinical efficacy was observed. Conclusion: Single-visit root canal treatment is a better option for treatment of pulpitis compared to multiple-sitting treatment.

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.

Aggressive Intra-Abdominal Fibromatosis in an Adolescent Girl - An Unusual Sequelae to Ovarian Germ Cell Tumor.

BACKGROUND: Abdominal fibromatosis presenting as an abdominal mass is a rare occurrence in a gynecological setting. The diagnosis might not be suspected preoperatively, and management could be challenging. CASE: An 18-year-old girl with ovarian germ cell malignancy was managed with staging laparotomy and chemotherapy. She developed a large abdominal mass 10 months later. An abdominopelvic mass (40 × 20 cm) was removed at laparotomy. The histopathological diagnosis was intra-abdominal fibromatosis. A rapidly growing abdominal mass recurred postoperatively. After discussion with the tumor board, chemotherapy with methotrexate and vinblastine was started. The tumor was not responsive, and the patient succumbed after the second cycle of chemotherapy. SUMMARY AND CONCLUSION: Abdominal fibromatosis should be considered among the differential diagnoses of a rapidly growing abdominal mass after resection of an ovarian germ cell tumor.