Pranshu Mohindra

Non-Hodgkin lymphoma of the Waldeyer's ring: clinicopathologic and therapeutic issues

Extranodal non-Hodgkin lymphoma (NHL) in head and neck region is most commonly seen in the Waldeyers ring. Waldeyers ring is a unique subtype of mucosa associated lymphoid tissue (MALT), which shows rarity of low-grade or MALT-type lymphomas and a high incidence of diffuse large B cell lymphoma (DLBCL). The commonest histology is DLBCL with natural history similar to primary nodal NHL. However, high association with gastrointestinal involvement is reported. The diagnostic workup is similar to that of the usual nodal NHL, and in absence of a specific staging system, the Ann Arbor staging is followed. As compared with T-cell subtypes, B-cell phenotypes are less likely to present with mucosal ulceration, epitheliotropism and angioinvasion. Stage of disease, histology and use of combined modality treatment have been proposed as significant prognostic factors. Treatment has evolved from the use of extended field radiotherapy (RT) alone to the use of combined chemotherapy and RT leading to almost doubling of survival. Advances in pathology and further risk stratification of patients into prognostic groups could lead to the development of novel therapeutic strategies to improve outcome.

Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

PURPOSE Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. METHODS AND MATERIALS We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. RESULTS A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). CONCLUSIONS Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.

Monthly palliative pelvic radiotherapy in advanced carcinoma of uterine cervix

BACKGROUND Patients with locally advanced cervical cancer are often severely distressed with incessant vaginal bleeding, offensive discharge and pelvic pain and are in some instances are beyond curative potential. At our institution we routinely use monthly palliative pelvic radiotherapy for these patients. METHODS AND MATERIAL One hundred patients treated between 2000 & 2004 were included in this analysis. Patients were treated with parallel-opposed pelvic portals with megavoltage radiation monthly up to a maximum of three fractions (10 Gy/fraction). Patients with good response after second fraction were considered for intracavitary brachytherapy delivering 30 Gy to point A. Response was documented with regard to relief of bleeding, vaginal discharge and pelvic pain. The other aspects evaluated were patient compliance, disease response, toxicity and survival. RESULTS Sixty-eight percent had FIGO stage IIIB, 12% had stage IVA and 14% had IVB disease. Twenty patients had metastatic disease. The median symptom duration was 5 months. Majority (67%) presented with vaginal bleeding, followed by discharge (69%) and pelvic pain (48%). All patients received at least one fraction of palliative pelvic radiotherapy. Sixty-one patients received the second fraction and 33 the third. Five patients received an intracavitary application. The overall response rates in terms of control of bleeding, discharge and pain were 100%, 49% and 33% respectively. The treatment was generally well tolerated with a median survival of 7 months. CONCLUSIONS Monthly palliative pelvic radiotherapy results in satisfactory control of symptoms in patients with locally advanced carcinoma of cervix with acceptable complications.

Primary PNET of maxilla: an unusual presentation.

Primitive neuroectodermal tumors (PNETs) are a type of small round cell tumors developing from migrating embryonal cells of the neural crest. Peripheral primitive neuroectodermal tumors (pPNETs) are less common with varying incidence of occurrence in head and neck region. Only 8 reported cases of primary PNET of maxilla are available in English literature. We report a case of 8-year-old boy diagnosed as pPNET of maxilla after detailed radiologic, histopathologic, including immuno-histochemical examination and molecular diagnosis using reverse transcription-polymerase chain reaction showing EWS-FLI1 translocation. The boy was treated with multiagent combination chemotherapy to be followed by definitive radiation therapy. A brief literature review of diagnosis and management of the previous 8 reported cases is done. In view of no definitive guideline for management of such cases, treatment on the lines of other pPNET is suggested.

Isolated non-Hodgkin's lymphoma of the pancreas: Case report and review of literature

BACKGROUND Isolated primary pancreatic lymphoma (PPL) is a rare extra-lymphatic non-Hodgkins lymphoma comprising less than 1% of all extra-lymphatic lymphomas. It is seen in people of advanced age and there is a slight male preponderance. It is difficult to diagnose; the vague presenting symptoms and nonspecific laboratory/radiological findings make it difficult to differentiate the condition from pancreatic adenocarcinoma. Histopathological examination is of paramount importance to conclusively establish the diagnosis since the treatment involves lymphoma protocols, and prognosis and survival in PPL are considerably superior to that in adenocarcinoma pancreas. CASE REPORT We report a case of isolated PPL diagnosed after Tru-Cut biopsy and immunohistochemistry after a thorough staging workup. RESULT The patient was treated with multi-agent combination chemotherapy followed by radiotherapy. DISCUSSION A review of literature was done using a Medline search to determine the incidence and prevalence of isolated PPL and to note the diagnosis and management of previously reported cases. CONCLUSION An exceedingly rare entity, isolated PPLs need to be differentiated from pancreatic adenocarcinomas by histopathological evaluation since management is on the lines of other extralymphatic lymphomas and prognosis is significantly better.

Dose Optimization Study of AEOL 10150 as a Mitigator of Radiation-Induced Lung Injury in CBA/J Mice

AEOL 10150 is a catalytic metalloporphyrin superoxide dismutase mimic being developed as a medical countermeasure for radiation-induced lung injury (RILI). The efficacy of AEOL 10150 against RILI through a reduction of oxidative stress, hypoxia and pro-apoptotic signals has been previously reported. The goal of this study was to determine the most effective dose of AEOL 10150 (daily subcutaneous injections, day 1–28) in improving 180-day survival in CBA/J mice after whole-thorax lung irradiation (WTLI) to a dose of 14.6 Gy. Functional and histopathological assessments were performed as secondary end points. Estimated 180-day survival improved from 10% in WTLI alone to 40% with WTLI-AEOL 10150 at 25 mg/kg (P = 0.065) and to 30% at 40 mg/kg (P = 0.023). No significant improvement was seen at doses of 5 and 10 mg/kg or at doses between 25 and 40 mg/kg. AEOL 10150 treatment at 25 mg/kg lowered the respiratory function parameter of enhanced pause (Penh) significantly, especially at week 16 and 18 (P = 0.044 and P = 0.025, respectively) compared to vehicle and other doses. Pulmonary edema/congestion were also significantly reduced at the time of necropsy among mice treated with 25 and 40 mg/kg AEOL 10150 compared to WTLI alone (P < 0.02). In conclusion, treatment with AEOL 10150 at a dose of 25 mg/kg/day for a total of 28 days starting 24 h after WTLI in CBA/J mice was found to be the optimal dose with improvement in survival and lung function. Future studies will be required to determine the optimal duration and therapeutic window for drug delivery at this dose.

Radiation Oncology Residency Selection: A Targeted Assessment of Factor Importance Among Fourth-Year Medical Students

Fourth-year medical students (MS4s) have limited meaningful exposure to radiation oncology training programs and thus base their decision largely on a limited number of factors. The assessment of variables utilized by MS4s during the selection process has never formally been investigated. We sought to better understand the importance of factors assessed by MS4s during the process of residency selection to gain perspective, which might be useful to training programs and future applicants. An anonymous survey was developed to assess factor importance during the radiation oncology training program selection process (1-3). The survey was a multiple-item Likert scale (1 Z not at all important to 5 Z extremely important, critical) and was distributed to current MS4s and to those in postgraduate year 1 (PGY1s) (4). The data were analyzed by use of mean and median Likert values, with interquartile range for median values (5). Responses were obtained from 70 MS4/PGY1s. The respondents were 59 MD and 11 MD/PhD candidates/graduates. Of the respondents, 56 were male (80%) and 14 were female (20%). The data from all survey participants were analyzed as a group and by subgroups of MD versus MD/PhD. Program factors were arranged in order of decreasing relative importance for the entire group (Table 1). The factors of highest importance overall were “perceived happiness of residents” (mean 4.43), “geographic location” (mean 3.71), and “clinical research

Neutrophil‐Lymphocyte Ratio Is a Prognostic Marker in Patients with Locally Advanced (Stage IIIA and IIIB) Non‐Small Cell Lung Cancer Treated with Combined Modality Therapy

BACKGROUND Neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in localized and advanced non-small cell lung cancer (NSCLC). Increased systemic inflammation portends a poorer prognosis in cancer patients. We hypothesized that low NLR at diagnosis is associated with improved overall survival (OS) in locally advanced NSCLC (LANSCLC) patients. PATIENTS AND METHODS Records from 276 patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation with or without surgery between 2000 and 2010 with adequate data were retrospectively reviewed. Baseline demographic data and pretreatment peripheral blood absolute neutrophil and lymphocyte counts were collected. Patients were grouped into quartiles based on NLR. OS was estimated using the Kaplan-Meier method. The log-rank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR quartile groups. The Cox proportional hazards model was used for multivariable analysis. RESULTS The NLR was prognostic for OS (p < .0001). Median survival in months (95% confidence interval) for the first, second, third, and fourth quartile groups of the population distribution of NLR were 27 (19-36), 28 (22-34), 22 (12-31), and 10 (8-12), respectively. NLR remained prognostic for OS after adjusting for race, sex, stage, performance status, and chemoradiotherapy approach (p = .004). CONCLUSION To our knowledge, our series is the largest to demonstrate that baseline NLR is a significant prognostic indicator in LANSCLC patients who received definitive chemoradiation with or without surgery. As an indicator of inflammatory response, it should be explored as a potential predictive marker in the context of immunotherapy and radiation therapy. IMPLICATIONS FOR PRACTICE Neutrophil-lymphocyte ratio measured at the time of diagnosis was associated with improved overall survival in 276 patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) treated with definitive chemoradiation with or without surgery. To our knowledge, our series is the largest to demonstrate that baseline neutrophil-lymphocyte ratio is a significant prognostic indicator in locally advanced NSCLC patients who received definitive chemoradiation with or without surgery. Neutrophil-lymphocyte ratio is an inexpensive biomarker that may be easily utilized by clinicians at the time of locally advanced NSCLC diagnosis to help predict life expectancy.

Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC)

OBJECTIVES To determine the prognostic effect of Body Mass Index (BMI) in definitively treated locally advanced NSCLC patients. MATERIALS AND METHODS In this single institution retrospective cohort study, we evaluated 291 patients who were treated for locally advanced NSCLC from 2000 to 2010. They were stratified into four BMI groups based on World Health Organization criteria: underweight (<18.5kg/m2), normal weight (18.5 to <25kg/m2), overweight (25 to <30kg/m2), and obese (≧30kg/m2). Overall survival was analyzed by BMI group. RESULTS Baseline patient characteristics and treatment parameters were similar between obese and normal weight patients. Increasing BMI was associated with improved overall survival (P=0.011), even when underweight cases were excluded. There was a sustained 31%-58% reduction in mortality of obese relative to normal weight patients (HR 0.68±0.21, 0.61±0.19, and 0.42±0.19, for each year post-treatment respectively). Statin use after diagnosis was highly associated with increasing BMI (P<0.001) and predicted improved survival in a multivariate analysis (HR 0.60, 95% CI 0.41-0.89, P=0.011). CONCLUSION Obese patients in this retrospective study had significantly improved survival relative to normal weight patients. Our data suggest that the protective effect of obesity in locally advanced NSCLC is not solely due to short-term treatment effects, decreased smoking exposure, or poor prognostic factors from underweight patients. Notably, statin use was also associated with improved survival. Additional studies are needed to clarify the mechanisms and possible concomitant factors underlying the obesity paradox in NSCLC.

Assessing p16 Status of Oropharyngeal Squamous Cell Carcinoma by Combined Assessment of the Number of Cells Stained and the Confluence of p16 Staining: A Validation by Clinical Outcomes.

Human papillomavirus–related oropharyngeal squamous cell carcinoma (OPSCC) has favorable prognosis relative to other head and neck squamous cell carcinomas. Criteria for predicting human papillomavirus status based upon p16 staining, including difficult cases with partial staining patterns, have been developed; however, clinical validation of these criteria and the clinical significance of partial p16 staining have not been reported. Eighty-one archival OPSCC cases were initially stained for p16 by immunohistochemistry with clone G175-405. The percentage of p16+ cells and percentage of confluence of p16+ cells were categorized as 25%, 26% to 75%, or >75%. Of all cases, 16 (20%) had partial p16 expression, with 26% to 75% p16+ cells. Applying previously developed criteria of >75% p16+ cells or >50% positive cells with >25% confluence, 48 (59%) patients were categorized p16+ and demonstrated expected clinical characteristics and superior disease-free survival and overall survival (P<0.001) compared with p16− patients. By themselves, the partial staining patients had intermediate outcomes; however, separating the partial staining cases by degree of confluence showed that those with >75% confluence had superior disease-free survival (P=0.042). When the 16 original partial staining cases were re-stained with the alternative anti-p16 E6H4 clone, p16 status remained concordant for all cases, but only 3 of the 16 were interpreted as demonstrating partial staining. This report shows that the prevalence of partial p16 staining varies with the antibody utilized and clinically validates the application of a graded evaluation of both the number as well as confluence of positive cells for risk stratification of patients with OPSCC.