Varun K. Chowdhry

Osteosarcoma following single fraction radiation prophylaxis for heterotopic ossification.

Radiotherapy for prophylaxis of heterotopic ossification (HO) is commonly used in high risk patients following orthopedic surgery. While treatment is effective and can prevent morbidity associated with HO, with any dose of radiation there is a concern of a radiation induced malignancy. Here we a report a case of radiation induced osteosarcoma which developed 11 years after a single fraction of 700 cGy. We performed dosimetric analysis by superimposing the patient’s original treatment field on a CT scan performed after the diagnosis. The radiotherapy dose for this patient is lower than classically reported for radiation induced sarcomas. We identified greatest bony destruction that was thought to be the epicenter of the tumor, and this was specially contoured on the diagnostic CT scan. This volume appears to be located at the edge of the radiotherapy field. Fifty percent of the treated volume received 240 cGy, the mean dose was 333 cGy. There was a variation across the treatment volume, between 21.8 cGy and 717 cGy. While a rare complication, we stress the importance of informing regarding the risk of a radiation induced malignancy following HO prophylaxis.

Use of proton therapy for re-irradiation in pediatric intracranial ependymoma

BACKGROUND AND PURPOSE To report disease control, survival and treatment-associated toxicity with the use of proton therapy (PRT) for re-irradiation of intracranial ependymoma. MATERIALS AND METHODS Twenty patients underwent 33 PRT re-irradiation courses for recurrent or metastatic lesions between June 2004 and February 2015 at Massachusetts General Hospital. RESULTS The majority of patients were female (60%), with infratentorial tumors (90%), anaplastic histology (55%), and initially received 55.8 GyRBE (52.2-59.4) involved field (IF) PRT. First failure was local (55%), distant (30%) or both (15%) at a median time of 23.9 months (9.9-98.5) from first treatment. Salvage therapy included re-resection (75%), chemotherapy (60%) and IFPRT (70%) to a median dose 50.4 GyRBE (35-55.8) in the majority of patients. The median follow-up was 37.8 months (5.5-138.0). Three year OS and PFS are 78.6% (95% CI 67.6-89.6) and 28.1% (95% CI 15.6-40.6), respectively. Longer OS was significantly associated with surgical resection of recurrent disease (HR 9.19, 95% CI 1.27-66.44, p=0.028). The pattern of second failure after re-irradiation was directly related to the pattern of first failure (p<0.01). Three of 14 patients (21.4%) locally re-treated experienced grade 2 radiation-associated treatment change. CONCLUSIONS Proton therapy appears safe and efficacious for the re-treatment of recurrent intracranial ependymoma.

Recurrent meningeal sarcoma successfully treated with stereotactic radiosurgery

Primary intracranial meningeal sarcoma is a rare neurological malignancy without strong evidence-based treatment guidelines. The authors describe a boy with primary meningeal sarcoma who symptomatically presented at 10 months of age and was treated with primary resection. The patient had multifocal recurrence approximately 2 years later. Given the location and rapid progression of the disease, the boy was treated with gamma knife surgery. He had a complete radiographic response 3 years posttreatment. He attends school full time and enjoys good quality of life. Based on local control and response to radiosurgery, the authors suggest that multifocal meningeal sarcomas not amenable to resection can be effectively managed with stereotactic radiosurgery.

Complications From Computed Tomography–Guided Core Needle Biopsy for Patients Receiving Stereotactic Body Radiation Therapy for Early-Stage Lesions of the Lung

BACKGROUND Obtaining a tissue diagnosis has traditionally been standard practice before initiating therapy for early-stage non-small-cell lung cancer (NSCLC). In several recent studies from Europe and Asia, a substantial proportion of patients have received stereotactic body radiation therapy (SBRT) based only on the imaging characteristics of the suspicious lesion. The underlying assumption is that the risk of percutaneous needle biopsy may outweigh the benefits in a population that generally has underlying pulmonary dysfunction and other medical comorbidity. Nevertheless, there is limited information regarding biopsy-related complication rates in high-risk patients with early-stage NSCLC who are treated with SBRT. MATERIALS AND METHODS This was a retrospective review of outcomes after biopsy in patients treated with SBRT. Complications of percutaneous core needle biopsy were analyzed in relation to patient and tumor characteristics. Each biopsy event was analyzed independently for patients with multiple biopsies. RESULTS A total of 112 percutaneous biopsies were performed in 103 patients. Pneumothorax of any degree was observed in 40 patients (35%) (95% CI, 27%-45%), and 12 patients (10.7%) had a clinically significant pneumothorax requiring chest tube placement (95% CI, 6%-18%). The time to first fraction of SBRT was not different in patients who had a pneumothorax or placement of a chest tube. On multivariate analysis, age, performance status, smoking history, pack-years of smoking, chronic obstructive pulmonary disease history, and forced expiratory volume in the first second of expiration were not statistically significantly associated with chest tube placement. CONCLUSION Computed tomography-guided needle biopsy in a primarily medically inoperable patient population is safe, with an acceptable degree of complications.

Thoracolumbar spinal cord tolerance to high dose conformal proton–photon radiation therapy

PURPOSE To evaluate and understand the tolerance of the thoracolumbar spinal cord using equivalent uniform dose (EUD) and dose volume histogram (DVH) analysis after combined high dose photon-proton radiotherapy. MATERIALS AND METHODS A total of 68 patients were identified as having high dose radiotherapy, ⩾5900cGy (RBE) in the region of the thoracolumbar spinal cord, defined as extending inferiorly to L2. Pathological diagnosis for patients in this review included chordoma (50 patients, 53.1%), chondrosarcoma (28 patients, 29.8%), osteosarcoma (3 patients, 3.2%), other sarcoma (11 patients, 11.7%), and other (2 patients, 2.1%). Patient data were reviewed retrospectively, detailed dose volume histogram data (DVH) were available for 23 patients. Composite plans and DVH were constructed for both pre-operative and post-operative radiation therapy courses in MIM-Vista software, as available. Dose constraints to the center and surface of the cord were 5400cGy (RBE), and 6300cGy (RBE) respectively, and patients receiving concurrent chemotherapy received an eight percent dose reduction. Spinal cord toxicity was recorded using the RTOG/EORTC late effects scoring system. RESULTS Clinical and dosimetric data for each patient were analyzed. Median prescription dose was 7020cGy (RBE), range (5940-7820cGy (RBE)). Median follow-up was 12.9months. Five-year overall survival for all patients in this group was 88.7%, 95%CI (74.7-95.2). One patient suffered from transient paralysis following stem cell transplant for treatment of myelodysplastic syndrome. Other reasons for spinal cord injury following treatment included: local disease progression, noted in 7 patients (10.3%), and direct result of surgery, noted in 8 patients (11.8%). Freedom from neurological injury (RTOG Grade 2 or higher) at 5years was 92.9%(95%CI: 74.6-98.2), at 6years was 80.9%(95%CI: 55.3-92.7), and at 8years 80.9%(95%CI: 55.3-92.7). CONCLUSION Our clinical and dosimetric data suggest that the noted dose constraints are safe and acceptable with regard to spinal cord complications. Pre-existing disease characteristics, surgical complications, as well as tumor progression, appear to be more important factors when it comes to spinal cord toxicity.

Radiation-induced dermatitis with vemurafenib therapy

More than one-half of melanomas contain an activating mutation in the serine-threonine protein kinase B-RAF (BRAF) gene.1,2 This mutation drives the constitutive activation of the Ras/Raf/MEK mitogen-activated protein kinase (MAP-K) pathway, which has been implicated in melanoma initiation, progression, and metastasis. 3 Vemurafenib (PLX-4032) is a potent kinase inhibitor with specificity for the BRAF V600E mutation and has been shown to have antitumor activity in vitro4-6 and in phase 1 clinical study.7 A phase 3 trial of vemurafenib versus dacarbazine demonstrated an increase in overall and progression-free survival.8 The most frequent adverse effects of vemurafenib reported are arthralgias, skin reactions, and fatigue. The development of a rash of any severity has been reported to be in the range of 36%-52%, with 7%-8% of patients developing grade 3 toxicity.8,9 We report the case of a 46-year-old male with metastatic melanoma who was being treated with vemurafenib and developed grade 3 radiation dermatitis shortly after radiation therapy for vertebral metastases.

Long-term survival in a patient with metastatic oropharynx squamous cell carcinoma to liver

The traditionally held view is that the patients with metastatic disease cannot be cured and should be treated palliatively as it was believed that the patients will eventually succumb to the disease progression due to lack of effective treatments for systemic disease. In this article, we report our experience in a patient who was diagnosed with metastatic oropharynx squamous cell carcinoma to the liver, who has now survived five years since the original diagnosis, and is three years disease free. This case report illustrates the curative potential in selected patients with limited burden of metastatic disease with aggressive local therapy to all known sites of disease. It underscores the importance of imaging modalities in monitoring progression of disease, and most importantly illustrates the importance of multidisciplinary care for oncology patients.

A population-based study of prognosis and survival in patients with second primary thyroid cancer after Hodgkin lymphoma

Abstract Hodgkin lymphoma (HL) survivors are at increased risk of thyroid cancer (TC). We sought to determine whether increased risks of high-risk pathology or mortality are seen with thyroid cancer after HL (HL-TC) compared with first primary thyroid cancer (TC-1). From the Surveillance, Epidemiology and End Results (SEER) registry, we compared patient and tumor characteristics as well as survival outcomes between HL-TC and TC-1 and fit a multivariable Cox model to assess for a possible association between HL history and overall survival after TC. Among 139,297 TC-1 and 174 HL-TC patients, history of HL was not associated with anaplastic or sarcoma TC. Multivariable analyzes showed that history of HL was not associated with a difference in risk of death after TC (hazard ratio: 0.96, 95% confidence interval: (0.81, 1.13), p = .61). Despite a significantly increased risk of TC among HL survivors, prior HL is not associated with more aggressive pathologic subtypes or worse prognosis.

Intracranial Stereotactic Radiosurgery in High Risk Patients with Metastases from Radioresistant Primary Tumors

Traditionally radioresistant brain metastases including melanoma, renal cell carcinoma, and sarcoma have poor outcomes with supportive care and whole brain radiotherapy (WBRT) alone. Although recent advances in biologic and targeted agents have improved systemic disease control in some patients with melanoma and renal cell carcinoma, such agents have poor penetration and are relatively ineffective in controlling brain metastases. Nevertheless, the ability to provide biologically ablative doses of radiotherapy by radiosurgery still can yield excellent local control similar that found in classically non-radioresistant brain tumors. Although conventional radiobiological models suggest that these patients will not respond to conventionally fractionated radiation therapy treatment, stereotactic radiosurgery allows high doses of radiation to be delivered to the target, while minimizing dose to normal tissue. Here we present treatment strategies and clinical outcome data in the management of such patients. Given the excellent local control following radiosurgery in this group of patients we propose that radiosurgery provides a clinical benefit to this group of patients. The use of whole brain radiation therapy should be considered to improve local control, although can be omitted in selected groups of patients.

Dosimetric and Clinical Analysis of Retreatment of Vertebral Body Metastases Using Intensity Modulated Radiation Therapy

pancreatic tumors by mega-voltage cone beam CT (MV-CBCT) is frequently difficult and daily localization is often based on more easily seen adjacent bony anatomy. Fiducial markers implanted into pancreatic tumors serve as surrogates for daily tumor position and may more accurately represent absolute tumor position. The purpose of this study using MV-CBCT image-guided IMRT was to compare differences in daily shifts based on alignment to implanted fiducial markers vs. alignment to adjacent bony anatomy. Materials/Methods: Gold fiducial markers were placed into the primary pancreatic tumor under endoscopic ultrasound guidance in12 patients. Patients subsequently received image-guided intensity modulated radiation therapy (IG-IMRT) at Allegheny General Hospital (Pittsburgh, PA). The markers were visible on both planning CT and daily MVCBCT. MV-CBCT was performed prior to each fraction and shifts were calculated based on alignment to the fiducial markers. We retrospectively reviewed the archived MV-CBCT datasets and calculated shifts in lateral, longitudinal and vertical axes relative to the initial imaging plan based on alignment to adjacent bony anatomy for each fraction. These were compared to shifts based on alignment to fiducial markers. Results: 243 fractions were analyzed. Neither complications secondary to fiducial marker placement nor instances of fiducial migration were observed. The mean absolute difference in shifts between those based on fiducial markers and those from alignment to bony anatomy was 3 mm (range 0–13 mm), 6 mm (range 0–21 mm), and 3 mm (range 0–12 mm), in the lateral, longitudinal and vertical directions respectively. The mean 3-dimensional vector shift difference between markers vs. bony anatomy alignment was 8.6 mm. Sixty-four (26.3%) fractions had a shift difference of at least 1 cm in at least one axis and 96 (39.5%) had a 3dimensional vector shift of at least 1 cm. Conclusions: These data suggest that fiducial markers used in conjunction with MV-CBCT improve accuracy of daily target delineation compared to localization using adjacent bony anatomy. The magnitude of the shift differences we report are consistent withc those in other reports using gold markers implanted into pancreatic tumors in conjunction with portal imaging and to data using implanted electromagnetic transponders. The reasons for movement of pancreatic tumors relative to adjacent bony anatomy are unknown but may include daily variations in gastric distension or biliary drainage. Our series suggests that gold fiducial markers placed in pancreatic tumors under EUS-guidance are well-tolerated, easily visible on MV-CBCT and remain stably positioned in the tumor throughout the course of radiotherapy.