Glioma arising in the setting of mismatch repair deficiency-rare or are we missing it?

Germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) can be mono-allelic or biallelic, resulting in a Lynch syndrome (LS) or constitutional mismatch repair deficiency (CMMRD) syndrome respectively. Glioma arising in the setting of MMR deficiency is uncommon. We describe two pediatric patients with high-grade glioma (HGG) and associated MMR protein deficiency. On histomorphology both cases showed HGG with astrocytic morphology and prominent multinucleated tumor cells. On immunohistochemistry, the first case was negative for IDH1 p.R132H showed loss of ATRX and p53 positivity. The second case was positive for IDH1 p.R132H and p53, but showed retained expression of ATRX. The histomorphology in both cases and additionally IDH mutation with retained ATRX in the second case, prompted us to test for MMR protein deficiency which was carried out by immunohistochemistry (IHC). One case revealed an immunostaining pattern suggestive of CMMRD while the other was suggestive of LS. Both the cases showed good response to surgery and radio-chemotherapy in the follow-up available. Our cases highlight the importance of testing for MMR proteins by simple IHC, in the setting of appropriate clinical scenario, histopathological and immunohistochemical findings. The recognition of these tumors is extremely important to guide further treatment and prompt family screening.

Randomized Control Study of the Effects of Turmeric Mouthwash on Oral Health Status, Treatment-Induced Mucositis, and Associated Oral Dysfunctions Among Patients With Head and Neck Cancer.

BACKGROUND: Oral mucositis is the most severe and debilitating adverse effect of cancer treatment, resulting in inadequate nutritional intake, treatment disruptions, and dose alteration, leading to increased hospital costs and decreased tumor control. OBJECTIVE: The aim of this study was to determine the effectiveness of turmeric mouthwash on oral health status and onset and severity of treatment-induced oral mucositis and associated oral dysfunctions among head and neck cancer patients. METHODS: A randomized controlled design was adopted (CTRI/2018/06/014367). Turmeric mouthwash was administered to the experimental group (n = 46) and benzydamine mouthwash was given to the control group (n = 46). Oral health status and mucositis were graded using the Oral Health Assessment Tool and the World Health Organization oral toxicity criteria, respectively. Oral dysfunctions were measured by a patient-reported oral mucositis symptom scale and xerostomia short-form inventory. All outcome variables were measured weekly during the entire course of radiation therapy. RESULTS: Both groups were comparable with regard to their demographic and outcome variables ( P > .05). The incidence of intolerable mucositis in the control group was 100% compared with 17.8% in the experimental group. Repeated-measures analysis of variance demonstrated significant differences in the onset and severity of oral mucositis ( P = .001), oral health status ( P = .001), and oral dysfunctions ( P = .001) between the experimental and control groups. CONCLUSION: Turmeric mouthwash was effective in reducing the severity of oral mucositis and associated oral dysfunctions as compared with benzydamine mouthwash. IMPLICATIONS: Use of turmeric, a nontoxic and cost-effective intervention, can be an alternative to the traditional management of oral mucositis.

Preliminary clinical outcomes of patients treated with vaginal brachytherapy alone using multi-channel vaginal brachytherapy applicator in operated early-stage endometrial cancer.

BACKGROUND: Recommendations for adjuvant treatment for postoperative, early-stage endometrial cancer varies from observation through vaginal brachytherapy alone to pelvic radiation. While observation alone can lead to recurrence, external radiotherapy has increased morbidity. The aim of this study is to show our results with vaginal brachytherapy alone using a multichannel applicator for treatment of early-stage endometrial cancer. MATERIALS AND METHODS: Consecutive patients undergoing vaginal brachytherapy alone following surgery for early-stage endometrial cancer were examined. A Miami multichannel vaginal brachytherapy applicator was used to deliver HDR brachytherapy in 62 patients from May 2013 to June 2018. CT scan-based images guided planning. A dose of 5.5-6.5 Gy × 4 fractions was prescribed 5 mm from the surface of the applicator. RESULTS: At a median follow up of 19 months (6-48 months), 93% of patients treated were alive with no recurrence. Two patients had only local recurrence, and 1 was salvaged with external radiotherapy and chemotherapy. There was only one nodal failure and 2 distant failures. There was no grade 2 or higher vaginal, gastrointestinal or genitourinary toxicity. CONCLUSION: Vaginal brachytherapy alone using a multichannel applicator can be considered for early-stage endometrial cancers without compromising outcomes.

Single Institution Experience of Postoperative Electron Beam Radiation Therapy in the Treatment of Keloids.

PURPOSE: Surgical excision followed by postoperative radiation therapy is an accepted modality to prevent keloid recurrence. Our practice has been to use electron beam radiation postoperatively to prevent recurrence, and we share our experience with this method in this study. METHODS AND MATERIALS: Twenty-two patients with 40 keloids treated postoperatively with electron beam radiation at our institution from 2014 to 2019 were analyzed retrospectively. Electron beam radiation was used for treatment in all cases, and radiation was initiated within 24 hours of surgery. A dose of 20 Gy in 5 fractions was delivered to the postoperative scar in 95% of the sites, and 8 Gy to 10 Gy in a single fraction was delivered to the remaining 5%. The patients were followed up, and recurrences were documented. RESULTS: At a mean follow-up of 35 months (range, 7-66 months), local control and cosmesis were achieved in 90% (36 of 40) of the treated sites with electron beam radiation therapy delivered at a dose of 20 Gy in 5 fractions. All recurrent keloids were located on the anterior chest wall over the sternum. There was no difference in outcome based on age, sex, or keloid length. CONCLUSIONS: Electron beam radiation therapy is a feasible, convenient, and safe modality for postoperative treatment of keloids. It achieves excellent local control with no grade 3 or higher toxicities.

Outcomes of Computed Tomography-Guided Image-Based Interstitial Brachytherapy for Cancer of the Cervix Using GEC-ESTRO Guidelines.

Locally advanced cancer of the cervix is treated by concurrent chemoradiation followed by brachytherapy. Interstitial brachytherapy is used to treat large tumors with involvement of parametrium, post-hysterectomy, and narrow, conical vagina. The GYN GEC-ESTRO working group described target volume delineation and also 3D image-based planning using MRI and 3D dose-volume parameters for brachytherapy of carcinoma cervix. CT-based as compared to MR-based image-guided brachytherapy (IGBT) is much more feasible and practical because MR access is still difficult for most departments. This is a retrospective study done to assess the local control in cancer of the cervix, treated based on these guidelines and dose received by 2 cm3 of the rectum as defined by the GEC-ESTRO guidelines and its correlation with long-term toxicity. Sixty-three patients of cancer of the cervix received 45 Gy/25 fractions of external beam radiotherapy with concurrent weekly cisplatin followed by interstitial brachytherapy. A central tandem was inserted into the uterine cavity. The needles were inserted based on the concept of gross tumor volume (GTV), high-risk clinical target volume (HRCTV), and intermediate-risk CTV (IR CTV) as defined by the GYN GEC-ESTRO guidelines. All patients underwent CT-based planning. A dose of 6.5 Gy × 4 fractions was delivered in two sessions such that the HRCTV received a total dose of 26 Gy. Dose optimization was done to prevent 2 cm3 of rectum from receiving > 400 cGy (60% of prescribed dose) per fraction and 2 cm3 of bladder from receiving 500 cGy per fraction. At a median follow-up of 41.5 months (range 6-106 months), 74.6% (47/63) of the patients were alive, with no local, loco-regional, or distant metastasis. Loco-regional control rate was 88% (56/63). Eight percent (5/63) of the patients developed grade I proctitis which was managed conservatively. There was no grades II, III, or IV proctitis. There was no bladder or sigmoid toxicity. GEC-ESTRO guidelines can be modified for CT-based planning also with very minimal late toxicity without compromising local control.

How common is hypothyroidism after external radiotherapy to neck in head and neck cancer patients?

PURPOSE: To identify the occurrence of clinical and subclinical hypothyroidism among head and neck cancer patients receiving radiation to the neck and to justify routine performing of thyroid function tests during follow-up. MATERIALS AND METHODS: This is a prospective nonrandomized study of 45 patients of head and neck cancer, receiving radiotherapy (RT). Thyroid stimulating hormone and T4 estimations were done at baseline and at 4 months and 9 months following RT. RESULTS: Of the 45 patients, 37(82.2 %) were males and eight (17.8 %) were females. All patients received radiation to the neck to a dose of >40Gy. 35.6% received concurrent chemotherapy. Two patients underwent prior neck dissection. Fourteen patients (31.1%) were found to have clinical hypothyroidism (P value of 0.01). Five (11.1%) patients were found to have subclinical hypothyroidism with a total 19 of 45 (42.2%) patients developing radiation-induced hypothyroidism. Nine of 14 patients with clinical hypothyroidism were in the age group of 51 to 60 years (P=0.0522). Five of 16 patients who received chemoradiation and nine of 29 who received RT alone developed clinical hypothyroidism. Above 40 Gy radiation dose was not a relevant risk factor for hypothyroidism. CONCLUSION: Hypothyroidism (clinical or subclinical) is an under-recognized morbidity of external radiation to the neck which is seen following a minimum dose of 40 Gy to neck. Recognizing hypothyroidism (clinical or subclinical) early and treating it prevents associated complications. Hence, thyroid function tests should be made routine during follow-up.

Invasive thymoma with intraorbital metastases.

Thymomas are epithelial neoplasm of thymus and most common primary neoplasm of anterior and superior mediastinum affecting males and females equally. It occurs usually in the fifth to seventh decade. Approximately one-third of thymomas are invasive. Metastases to distant extrathoracic sites such as the liver, lung, lymph node, kidneys, ovary and brain occur infrequently. This is more common with invasive thymomas. Although brain has been shown to be a site of infrequent metastases, intraorbital metastases has not yet been reported. Here we report one such case of invasive thymoma of anterior superior mediastinum, which later metastasized to orbit as well as the brain.

Role of palliative radiotherapy in brain metastases.

BACKGROUND: Brain metastases are a common manifestation of systemic cancer and exceed primary brain tumors in number and are a significant cause of neurologic problems. They affect 20-40% of all cancer patients. Aggressive management of brain metastases is effective in both symptom palliation and prolonging the life. Radiotherapy has a major role to play in the management of brain metastases. AIM: The aim of the study was to know the outcome of palliative radiotherapy in symptomatic brain metastases in terms of improvement in their performance status. MATERIALS AND METHODS: This is a retrospective study of 63 patients diagnosed to have brain metastases and treated with palliative whole brain radiotherapy to a dose of 30 Gy in 10 fractions over two weeks between June 1998 and June 2007. Diagnosis was done in most of the cases with computed tomography scan and in a few with magnetic resonance imaging. Improvement in presenting symptoms has been assessed in terms of improvement in their performance status by using the ECOG scale. RESULTS: Fifty-four patients completed the planned treatment. Eight patients received concurrent Temozolamide; 88% of patients had symptom relief at one month follow-up; 39/54 patients had a follow-up of just one to three months. Hence survival could not be assessed in this study. CONCLUSION: External beam radiotherapy in the dose of 30 Gy over two weeks achieved good palliation in terms improvement in their performance status in 88% of patients. Addition of concurrent and adjuvant Timozolamide may improve the results.