Nikhil Yegya-Raman

A Case of Sporadic Creutzfeldt-Jakob Disease Presenting as Conversion Disorder

Background. Creutzfeldt-Jakob disease is a rare disorder of the central nervous system. Its initial diagnosis may be obscured by its variable presentation. This case report illustrates the complexity of diagnosing this disease early in the clinical course, especially when the initial symptoms may be psychiatric. It offers a brief review of the literature and reinforces a role for consultation psychiatry services. Methods. PUBMED/MEDLINE was searched using the terms “Creutzfeldt-Jakob disease”, “psychiatric symptoms”, “conversion disorder”, “somatic symptom disorder”, “functional movement disorder”, and “functional neurologic disorder”. Case. The patient was a 64-year-old woman with no prior psychiatric history who was initially diagnosed with conversion disorder and unspecified anxiety disorder but soon thereafter was discovered to have Creutzfeldt-Jakob disease. Discussion. This case highlights the central role of psychiatric symptoms in early presentations of Creutzfeldt-Jakob disease. Still, few other cases in the literature report functional neurological symptoms as an initial sign. The consultation psychiatrist must remain alert to changing clinical symptoms, especially with uncharacteristic disease presentations.

Association of Target Volume Margins With Locoregional Control and Acute Toxicities for Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiation Therapy

PURPOSE This study aimed to investigate the association between target volume margins and clinical outcomes for patients with inoperable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy. METHODS AND MATERIALS We reviewed the records of 82 patients with inoperable NSCLC treated between 2009 and 2016 with concurrent chemoradiation. All patients received positron emission tomography-based treatment planning, 4-dimensional computed tomography simulation to define an internal target volume, and daily cone beam computed tomography. We quantified variations in target volume margins with a margin deviation index (MDI), calculated as the percentage change in equivalent uniform dose between the original planning target volume (PTV) and a standard reference PTV 10 mm beyond the original gross tumor volume, consistent with the minimum margins mandated by recent NSCLC trials. Greater MDIs equated to smaller effective target volume margins. We dichotomized patients by the upper tercile MDI value (5.8%). Endpoints included time to locoregional progression and time to grade ≥ 3 radiation esophagitis (RE3) or radiation pneumonitis (RP3), modelled with the Fine-Gray method. RESULTS Median follow-up was 37.8 months (range, 5.9-58.1 months). Larger MDIs correlated with smaller clinical target volume (CTV) + PTV margins, larger gross tumor volumes, later treatment year, and intensity modulated radiation therapy use. The risk of locoregional progression did not differ for MDI ≥5.8% versus <5.8% (adjusted hazard ratio: 0.88; P = .76), but the risk of RE3 or RP3 was decreased for MDI ≥5.8% (adjusted hazard ratio: 0.27; P = .027). Patients with MDI ≥5.8% were treated with smaller CTV + PTV margins (median, 5.6 vs 8 mm; P < .0001) and a marginally lower volume of esophagus receiving ≥50 Gy (median, 31.1% vs 35.3%; P = .069). CONCLUSIONS Smaller margins were used for larger tumors but were not associated with an increase in locoregional failures. Additional studies could clarify whether smaller margins, when used alongside modern radiation therapy techniques, decrease treatment-related toxicity for inoperable NSCLC.

Multiple primary malignancies in patients with anal squamous cell carcinoma

Prior studies examining the risk of second primary malignancy (SPM) after a first primary cancer generally have used large datasets such as the Surveillance, Epidemiology, and End Results (SEER) registry and excluded survivors of previous primaries and developers of synchronous primaries. The goal of this study was to provide a more complete representation of multiple cancer risk in squamous cell carcinoma of the anus (SCCA) patients. A single-institution retrospective study of 46 patients treated definitively for SCCA between January 2006 and July 2017 was conducted. Of the 46 patients, 18 (39%) had either a primary malignancy before SCCA (n=9) or SPM after an index SCCA (n=9). Six patients had ≥3 total malignancies. In our cohort, patients without SPMs tended to die from SCCA recurrence, while patients with SPMs were more likely to die from their SPM than from SCCA. Our study suggests that patients with SCCA are often either survivors of previous cancers or develop later malignancies. Several risk factors may play a role including HPV infection, HPV-related or treatment-related immunosuppression, somatic mutations due to chemotherapy, and genetic factors. Patients with SCCA require lifelong surveillance given their elevated risk of malignancy. Future work should focus on identifying genomic or immunologic factors that may predispose SCCA patients to develop multiple primary malignancies.

Dosimetric Predictors of Symptomatic Cardiac Events After Conventional-Dose Chemoradiation Therapy for Inoperable NSCLC

Introduction: We hypothesized that higher cardiac doses correlates with clinically significant cardiotoxicity after standard‐dose chemoradiation therapy (CRT) (˜60 Gy) for inoperable NSCLC. Methods: We retrospectively reviewed the records of 140 patients with inoperable NSCLC treated with concurrent CRT from 2007 to 2015. Extracted data included baseline cardiac status, dosimetric parameters to the whole heart (WH) and cardiac substructures, and the development of post‐CRT symptomatic cardiac events (acute coronary syndrome [ACS], arrhythmia, pericardial effusion, pericarditis, and congestive heart failure [CHF]). Competing risks analysis was used to estimate time to cardiac events. Results: Median follow‐up was 47.4 months. Median radiation therapy dose was 61.2 Gy (interquartile range, 60 to 66 Gy). Forty patients (28.6%) developed 47 symptomatic cardiac events at a median of 15.3 months to first event. On multivariate analysis, higher WH doses and baseline cardiac status were associated with an increased risk of symptomatic cardiac events. The 4‐year cumulative incidence of symptomatic cardiac events was 48.6% versus 18.5% for mean WH dose ≥ 20 Gy versus < 20 Gy, respectively (p = 0.0002). Doses to the WH, ventricles, and left anterior descending artery were associated with ACS/CHF, whereas doses to the WH and atria were not associated with supraventricular arrhythmias. Symptomatic cardiac events (p = 0.0001) were independently associated with death. Conclusions: Incidental cardiac irradiation was associated with subsequent symptomatic cardiac events, particularly ACS/CHF, and symptomatic cardiac events were associated with inferior survival. These results support the minimization of cardiac doses among patients with inoperable NSCLC receiving standard‐dose CRT.

Advanced radiation techniques for locally advanced non-small cell lung cancer: intensity-modulated radiation therapy and proton therapy

Radiation therapy (RT) represents an integral part of a multimodality treatment plan in the definitive, preoperative and postoperative management of non-small cell lung cancer (NSCLC). Technological advances in RT have enabled a shift from two-dimensional radiotherapy to more conformal techniques. Three-dimensional conformal radiotherapy (3DCRT), the current minimum technological standard for treating NSCLC, allows for more accurate delineation of tumor burden by using computed tomography-based treatment planning instead of two-dimensional radiographs. Intensity-modulated RT (IMRT) and proton therapy represent advancements over 3DCRT that aim to improve the conformity of RT and provide the possibility for dose escalation to the tumor by minimizing radiation dose to organs at risk. Both techniques likely confer benefits to certain anatomic subgroups of NSCLC requiring RT. This article reviews pertinent studies evaluating the use of IMRT and proton therapy in locally advanced NSCLC, and outlines challenges, indications for use, and areas for future research.

Radiation Therapy for Tracheobronchial Metastases from Head and Neck Squamous Cell Carcinoma

Tracheobronchial metastases from head and neck squamous cell carcinoma (HNSCC) represent a rare occurrence, with few reported cases in the literature. Here, we present two patients with HNSCC who developed tracheobronchial metastases at different time points in their disease course. Patient 1 presented with a localized tonsillar primary, underwent tonsillectomy and post-operative radiation therapy to the tumor bed and bilateral neck, and experienced multiple subsequent metastases in different locations throughout the tracheobronchial tree. Each time, she received surgery and/or chemoradiation therapy to the metastatic lesion(s). Patient 2 presented with a supraglottic primary metastatic to the carina and both mainstem bronchi, and, based on patient 1’s recurrence pattern and a suspicion for direct tumor extension, was treated upfront with definitive chemoradiation from the supraglottis down through much of the tracheobronchial tree. A year out from treatment, patient 2 has achieved excellent locoregional control with few treatment-related toxicities but unfortunately has developed new liver metastases not seen on pre-treatment imaging. This case highlights the difficulty in ascertaining the extent of metastatic spread for HNSCC patients with isolated tracheobronchial metastases and describes our approach to delivering curative-intent radiation therapy.

Variations in Initiation Dates of Chemotherapy and Radiation Therapy for Definitive Management of Inoperable Non–Small Cell Lung Cancer Are Associated With Decreases in Overall Survival

&NA; Concurrent chemoradiation therapy (CRT) is the standard of care for non–small cell lung cancer. We studied the effects of minor differences in the CRT start dates in a cohort of 11,119 patients and found that minimal differences, as few as 3 days, were associated with worse survival rates. Efforts to mitigate the factors that interfere with the synchronous delivery of CRT are needed. Background: We evaluated trends in administration of concurrent chemoradiation therapy (CRT) and how variations in start dates of chemotherapy and radiotherapy affected overall survival (OS) in patients with non–small cell lung cancer (NSCLC) undergoing a course of definitive CRT. Materials and Methods: Cases of NSCLC treated with definitive CRT were obtained from the National Cancer Database. A survival analysis was performed with Kaplan‐Meier curves and Cox proportional hazards models. Propensity score matching was conducted. Results: On a national level, only 48.6% of patients began concurrent CRT on the same day. In a propensity‐matched population, starting CRT within 6 days was associated with improved OS (17.9 months) compared with starting 7 to 13 days apart (16.5 months; P = .04). Starting dual therapy within 6 days of each other was associated with a 7% reduction in the risk of death (hazard ratio, 0.93; P = .05). Furthermore, in a propensity‐matched cohort, starting CRT within 3 days was associated with longer survival (18.7 months) compared with 4 to 6 days apart (17.5 months; P = .02). Starting treatment 4 to 6 days apart was associated with an 8% increased risk of death (hazard ratio, 1.08; P = .04). Conclusion: A large proportion (48.6%) of patients with unresectable NSCLC do not initiate CRT on the same day as is considered standard by national guidelines. In this population, nonsimultaneous initiation of CRT was associated with differences in OS. Further efforts to understand the mitigating factors and barriers that interfere with timely delivery of concurrent CRT are needed.

Corrigendum to “A Case of Sporadic Creutzfeldt-Jakob Disease Presenting as Conversion Disorder”

[This corrects the article DOI: 10.1155/2017/2735329.].

Acute Suppurative Thyroiditis in an Intravenous Drug User with a Preexisting Goiter

Acute suppurative thyroiditis (AST) is an uncommon, potentially life-threatening cause of a rapidly enlarging neck mass. It may present similarly to subacute thyroiditis, a relatively benign and self-limiting condition. We report a case of AST in an adult intravenous (IV) drug user with a preexisting goiter who presented with a left forearm abscess that grew methicillin-sensitive Staphylococcus aureus. In this particular case, clinical suspicion for AST was high. As a result, early IV antibiotic therapy was initiated, and this led to rapid clinical improvement furthermore preventing airway compromise. To our knowledge, this is the first case of AST in the literature resulting from likely hematogenous spread in the setting of IV drug use and a preexisting goiter. Overall, this case highlights the importance of assessing risk factors for AST in patients whose presentations may seem more typical of subacute thyroiditis. Such an approach will lead to timely diagnosis and treatment to avoid potentially devastating consequences.

Adjuvant therapeutic strategies for resectable pancreatic adenocarcinoma

Of all patients diagnosed with pancreatic adenocarcinoma, only 15-20% present with resectable disease. Despite curative-intent resection, the prognosis remains poor with the majority of patients recurring, prompting the need for adjuvant therapy. Historical data support the use of adjuvant 5-fluorouracil (5-FU) or gemcitabine, but recent data suggest either gemcitabine plus capecitabine or modified FOLFIRINOX can improve overall survival when compared to gemcitabine alone. The use of adjuvant chemoradiation therapy remains controversial, primarily due to limitations in study design and mixed results of historical trials. The ongoing Radiation Therapy Oncology Group (RTOG)-0848 trial hopes to further define the role of adjuvant chemoradiation therapy. Intraoperative radiation therapy (IORT) and adjuvant immunotherapy represent additional possibilities to improve outcomes, but evidence supporting their use is limited. This article reviews adjuvant therapeutic strategies for resectable pancreatic adenocarcinoma, including chemotherapy, chemoradiation therapy, IORT and immunotherapy.