Primary intracranial extra-skeletal myxoid chondrosarcoma of right lateral ventricle with EWSR1 gene fusion: a case report and review of literature.

BACKGROUND: Primary intracranial malignancies with extra-skeletal myxoid chondrosarcoma (EMC) features are extremely rare. EMC constitutes a distinct genomic entity characterised by reciprocal translocation of fusion genes, most commonly EWS RNA Binding Protein 1 (EWSR1) in 22q12 with Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) in 9q2-q31.1. It is reported to have a high propensity for local recurrence and has potential for metastasis. So far in 28 years since its first description, only 17 cases of primary intracranial EMC were reported in literature. This would be the second case of intraventricular origin and first case from lateral ventricle. CASE PRESENTATION: A 27-year-old male presenting with complaints of headache, seizures and pain in neck was diagnosed to have a mass lesion in right lateral ventricle in Magnetic Resonance Imaging of brain. He underwent right parieto-occipital craniotomy with total excision of the lesion. Initial histopathological examination was reported as Ependymoma, WHO grade II. However, blocks and slides review with immunohistochemistry (IHC) markers revealed neoplastic aetiology with extensive myxoid changes. Hence, fluorescent in-situ hybridisation (FISH) testing was done with EWSR1 break apart probe, which demonstrated EWSR1 break apart signals. Therefore, correlating the clinical findings with morphology, IHC and FISH, the diagnosis of primary intracranial EMC was rendered. Patient received adjuvant external beam radiation of 54 Gy in 30 fractions to the post-op region. At 29-month follow-up, there was no evidence of disease recurrence. CONCLUSIONS: Owing to the rarity of the condition, there are no standard treatment guidelines available for primary intracranial EMC. A combined treatment approach with surgery followed by adjuvant radiotherapy provides good local control with less morbidity.

Total body irradiation of bone marrow transplant using helical TomoTherapy with a focus on the quality of dose contribution at junction target volumes.

PURPOSE: Total body irradiation (TBI) can be safely delivered on TomoTherapy (Accuray, Sunnyvale, CA, USA) in both pediatric and adult patients with proper imaging and planning despite the length constraint of 135 cm. To overcome this limitation, two CT (Computed Tomography) scans (CT1& CT2) are taken in patients above 135 cm in height. Adequate junction dose coverage is important in TBI. Presently, there is no clinical report with a focus on the quality of dose distribution at the CT junction in view of the guidelines on quality of coverage from the RTOG. Hence, our main objectives were to evaluate the dose distribution and quality of coverage at the junction in 16 patients who received TBI using TomoTherapy. METHODS: PTV(upper) and PTV(lower) along with a junction were created on CT1 and CT2, respectively. Subsequently, the 10 cm junction in the thigh region was divided into five target volumes of 2 cm thickness with dose prescription ranging from 10 to 90% to deliver a total dose equal to 100% when fused. RESULTS: The D50 was equal to the prescribed dose in most of the cases ranging from 99.5 to 104% for PTV(upper), 100-103% for PTV(lower), and 99.5-108% for junctional PTVs (1PTV, 2PTV, 3PTV, 4PTV, and 5PTV). The average D95 doses from PTV(upper) and PTV(lower) were 97 ± 1.4% and 96.7 ± 1.08%, respectively. The average D95 doses for 1PTV, 2PTV, 3PTV, 4PTV, and 5PTV were 96.1 ± 1.88%, 91.6 ± 1.82%, 87.3 ± 1.5%, 91.6 ± 1.4%, and 96.2 ± 1.5% respectively. QRTOG values ranged between 0.85 and 1.05 and were in concordance with RTOG guidelines. CONCLUSION: Since junction-based planning was required for most TBI patients, it is essential to evaluate the quality of dose coverage in the junction for better TBI plans.

Influence of neoadjuvant therapy on outcomes in patients with resectable carcinoma of esophagus and gastro-esophageal junction from a tertiary cancer care center in India.

BACKGROUND AND OBJECTIVES: The aim of this study is to compare the outcomes of neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT) followed by surgery to upfront surgery (surgery alone) in patients with resectable carcinoma of the esophagus (esophageal cancer [EC]), and gastro-esophageal junction (GEJ) in a limited resource setting. METHODS: A retrospective analysis of a prospectively maintained database was performed to identify patients (from January 2010 through December 2016) who underwent surgery for EC and GEJ cancers. RESULTS: A total of 454 patients were included and categorized into the following groups: nCT (n = 65), nCRT (n = 152) and upfront surgery (n = 237). Squamous cell carcinoma and adenocarcinoma accounted for two-thirds and one-third of the cases, respectively. nCRT group patients were also noted to have smaller tumors, lower margin positivity and a higher R0 resection rates. With a median follow up of 76 months (35-118 months) improved 5-year overall survival was noted in nCRT group in comparison to nCT and upfront surgery groups (56.5% vs. 34% and 35%, respectively, p = .021). CONCLUSIONS: The results of our study demonstrate the beneficial effect of nCRT for patients with EC and GEJ in a limited resource setting. Further studies are required to analyze and promote the benefits of nCRT in limited-resource settings.

Fundamentals to clinical application of nanoparticles in cancer immunotherapy and radiotherapy.

Cancer immunotherapy has made rapid progress over the past decade leading to high enthusiasm and interest worldwide. Codelivery of immunomodulators with chemotherapeutic agents and radioisotopes has been shown to elicit a strong and sustained immune response in animal models. Despite showing promising results in metastatic and recurrent cancers, the utilisation of immunotherapy in clinical settings has been limited owing to uncertainties in elicited immune response and occurrence of immune-related adverse events. These uncertainties can be overcome with the help of nanoparticles possessing unique properties for the effective delivery of targeted agents to specific sites. Nanoparticles play a crucial role in the effective delivery of cancer antigens and adjuvants, modulation of tumour microenvironment, production of long-term immune response and development of cancer vaccines. Here, we provide a comprehensive summary of nanotechnology-based cancer immunotherapy and radiotherapy including basics of nanotechnology, properties of nanoparticles and various methods of employing nanoparticles in cancer treatment. Thus, nanotechnology is anticipated to overcome the limitations of existing cancer immunotherapy and to effectively combine various cancer treatment modalities.

Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment.

OBJECTIVE: The objective of this study was to evaluate the incidence of hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated primarily with surgery. MATERIALS AND METHODS: A retrospective review was carried out to analyze hypothyroidism incidence and its relation to adjuvant treatment (radiation/radio-chemotherapy) in oral tongue carcinoma after the primary surgical ablation and neck dissection. Hypothyroidism was analyzed in relation with dose of radiation, gender, and adjuvant treatment modality. RESULTS: The study analyzed the patients who were treated between January 2012 and June 2015. Among 705 patients with carcinoma of the tongue treated primarily with wide local excision and neck dissection, 383 received adjuvant treatment. A total of 215 patients received radiation, and 168 received concurrent radio-chemotherapy. Of 378 patients, 78 developed hypothyroidism during follow-up: 27 patients received concurrent radio-chemotherapy, and the remaining 51 received only radiation. Lower neck received 40-48 Gy in 2 patients, 50 Gy in 74 patients, and 60-70 Gy and concurrent radio-chemotherapy in 27 patients. Median follow-up was 32 months. Hypothyroidism occurred in 21.5% of patients with squamous cell carcinoma of the oral tongue. The minimum period to develop hypothyroidism was 3 months in this study. Gender and adjuvant treatment were not found to be significant for the incidence of hypothyroidism. CONCLUSIONS: A significant number of patients with carcinoma of the tongue who receive adjuvant treatment will develop hypothyroidism, hence frequent monitoring of thyroid function is advised during follow-up.

Assessment of monitor unit limiting strategy using volumetric modulated arc therapy for cancer of hypopharynx.

PURPOSE: To quantify relative merit of MU deprived plans against freely optimized plans in terms of plan quality and report changes induced by progressive resolution optimizer algorithm (PRO3) to the dynamic parameters of RapidArc. MATERIALS AND METHODS: Ten cases of carcinoma hypopharynx were retrospectively planned in three phases without using MU tool. Replicas of these baseline plans were reoptimized using "Intermediate dose" feature and "MU tool" to reduce MUs by 20%, 35%, and 50%. Overall quality indices for target and OAR, integral dose, dose-volume spread were assessed. All plans were appraised for changes induced in RapidArc dynamic parameters and pre-treatment quality assurance (QA). RESULTS: With increasing MU reduction strength (MURS), MU/Gy values reduced, for all phases with an overall range of 8.6-34.7%; mean dose rate decreased among plans of each phase, phase3 plans recorded greater reductions. MURS20% showed good trade-off between MUs and plan quality. Dose-volume spread below 5Gy was higher for baseline plans while lower between 20 and 35Gy. Integral dose was lower for MURS0%, not exceeding 1.0%, compared against restrained plans. Mean leaf aperture and control point areas increased systematically, correlated negatively with increasing MURS. Absolute delta dose rate variations were least for MURS0%. MU deprived plans exhibited GAI (>93%), better than MURS0% plans. CONCLUSION: Baseline plans are superior to MU restrained plans. However, MURS20% offers equivalent and acceptable plan quality with mileage of MUs, improved GAI for complex cases. MU tool may be adopted to tailor treatment plans using PRO3.

Promise of uterine transplant--myth or a reality?

The scientific basis of uterus transplantation has been developing in parallel to other organ transplants throughout the modern period of transplant medicine. Immunosuppression and surgical techniques have been adequate for at least a decade; ethics and society have been less clearly developed. To many observers, it is still unclear if the endeavor is an overall positive or negative. Although scientific and technical challenges have been overcome, the ethical determinations will be a dynamic process while more experience continues to be gained. The most significant experience still lacking is a term gestation. Undoubtedly during a nine-month gestation, unforeseen challenges will test scientific processes and ethical assumptions. Despite dozens of animal experiments and a few animal births, no human birth has occurred to allow any definitive conclusions.

Study of positional dependence of dose to bladder, pelvic wall and rectal points in High-Dose-Rate Brachytherapy in cervical cancer patients.

The objective of the study is to examine the variation in doses to, Bladder, pelvic wall and Rectal Points when a patient is simulated in Supine (S Position) and Lithotomy M shaped positions (LM Position), respectively as part of Intracavitary Brachytherapy in Cervical Cancer patients. Patients (n = 19) were simulated and orthogonal images were taken in S Position and LM Positions on a physical simulator. Digital orthogonal X-ray images were transferred to Brachyvision Treatment Planning System via Dicom to generate treatment plans. Radio opaque dye of 7 ml was injected into the Foley bulb for identification and digitization of International Commission on Radiological Units and Measurements (ICRU) Bladder point. Pelvic side wall points were marked in accordance with ICRU 38 recommendations. A Rectal tube containing dummy source marker wire was used to identify Rectal Point. Students't-test was used to analyze the results. Doses in LM Position were lower and statistically significant when compared to S Position for ICRU Bladder Point, pelvic walls and Rectal Point. It was observed that movement of applicator could be the reason for the variations in doses between the two positions. Bladder, pelvic wall and rectal points systematically registered lower doses in LM Position as compared to S Position.

Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia.

OBJECTIVE: Standard surgical treatment for CIN may impair fertility generating a need for alternative treatment options. We tested the efficacy and toxicity of oral DIM in the treatment of CIN 2 or 3 lesions. METHODS: Patients with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or 3 scheduled for loop electrosurgical excision procedure (LEEP) were randomized 2:1 to receive diindolylmethane (DIM) (BioResponse-DIM, BioResponse, Boulder, CO) orally at approximately 2 mg/kg/day for 12 weeks or placebo (defatted rice bran, BioResponse). Subjects were evaluated every 3-4 months for 1 year. Analysis of data up to 1 year was assessed including Pap smear, HPV, colposcopy, biopsy and physical examination were performed at follow-up. Central pathology review confirmed all histology diagnoses. RESULTS: To date, 64 subjects (mean age 28 years, range 18-61) have been enrolled (45 in the DIM arm, 19 in the placebo arm), with 60 available for analysis. Average follow-up was 6 months. At enrollment, 58% were diagnosed with CIN 2 and 42% with CIN 3, 57% of subjects were Caucasian, 15% African American, 12% Hispanic and 17% Asian. During treatment 2 subjects (3%) complained of nausea (grade 2) at the 3- to 4-month visit. No systemic toxicities were observed (normal CBC, LFTs, comprehensive metabolic). Forty-six subjects had biopsies at first follow-up (77%). Twenty-one subjects (47%) in the DIM group had improved CIN with a decrease by 1-2 grades or a normal result. Median time to improvement was 5 months. Improved Pap smear was seen in 49% (22/45) with either a less severe abnormality or normal result. Colposcopy improved in twenty-five subjects in the DIM group (56%). Of these 25 subjects, 21 (84%) had improved colposcopic impression, 13 (52%) had a decrease in involved quadrants and 18 (72%) had a decrease in lesion number. Complete colposcopic response was observed in 4 subjects (9%). Stratifying by level of dysplasia, age, race, HPV status, tobacco use, contraceptive used did not alter the results. At median follow-up of 6 months, 85% of subjects have not required LEEP based on routine clinical triage of improving global assessment. There was no statistically significant difference in any outcome between the DIM and placebo group. CONCLUSION: Oral DIM at 2 mg/kg/day is well tolerated with no significant toxicity. We observed a high rate of clinically significant improvement in confirmed CIN 2 or 3 lesions among both treatment groups in this randomized clinical trial.

Comparison of endometrial aspiration biopsy techniques: specimen adequacy.

OBJECTIVE: To compare adequacy of specimens obtained by 3 different endometrial aspiration biopsy techniques--corkscrew, modified dilatation and curettage (D&C) and a combination of both, with or without povidone-iodine cervical cleansing. STUDY DESIGN: A retrospective chart review of a single group practice using a single endometrial aspiration biopsy device for all 3 techniques. Each attending indicated their method of use with the device. For diagnostic purposes, specimen adequacy was categorized as "satisfactory," "suboptimal" and "insufficient." RESULTS: There were 66 corkscrew, 71 modified D&C and 55 biopsies performed using the combined technique. Mean age was 48; 62.5% were premenopausal and 89% had a normal-sized uterus. Postmenopausal patients were more likely than younger women to have suboptimal or insufficient samples, 27% vs. 11%, respectively. Using the combined technique was better (95%) than the corkscrew alone (77%) for satisfactory specimens. Diagnosis was possible in 90% of specimens. CONCLUSION: The combined technique appears to be better than using either technique alone. Povidone-iodine cervical cleansing is safe but may be unnecessary. Because of the large numbers of endometrial biopsies performed yearly, even a small difference in test characteristics can have significant clinical ramifications.

Decreased breast cancer rates among women with choriocarcinoma.

OBJECTIVE: We hypothesized that exposure to high levels of hCG in women diagnosed with choriocarcinoma would decrease future breast cancer risk. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) registry limited-use database (1973-2004) to search for placenta tumors (ICD-10 C58), i.e. choriocarcinoma (CC). Demographics were obtained including patient ID, primary site, year of diagnosis, sex, race, DOB, age group and survival months. Patients with initial choriocarcinoma were searched for subsequent breast cancers. The cohort diagnosis with CC and subsequent breast cancers were compared to general population-based rates of breast cancer. RESULTS: A query for CC yielded 646 women between the ages 15 and 54 years. Of the 646 women, 422 were white, 129 African-American, and 95 "other". Total women-years of observation were 7165.3 with two CC patients developing breast cancer yielding a breast cancer incidence rate of 27.9/100,000 women-years. The incidence rate ratio(IRR) of the CC cohort to the general population was 0.21 (95% CI(0.145-0.327); P<0.01). In women with CC under the age of 35 years the breast cancer rate was 34.1/100,000, IRR 0.27 (95% CI(0.182-0.386); P<0.01). Controlling for race, breast cancer rates in whites were 49.3/100,000 (IRR 0.37, P<0.01); in African-American 1.3/100,000 (IRR 0.01, P<0.001); and 2.6/100,000 (IRR 0.03, P<0.001) in "others" compared to the general population. CONCLUSION: Women with prior CC had a 79% reduction in breast cancer risk compared to the general population regardless of age and race. Given the high level of hCG and decreased rate of breast cancer among women with CC, the hypothesis that hCG is protective against breast cancer seems plausible.