Proposed prognostic scoring system evaluating risk factors for biochemical recurrence of prostate cancer after salvage radiation therapy.

OBJECTIVE: To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/mL and rising as the definition of BCR. PATIENTS AND METHODS: We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks (RRs) from multivariable Cox regression models. RESULTS: With a median follow-up of 5.5 years after SRT, 354 patients (61%) experienced BCR. At 5 years after SRT, 40% of patients were free of BCR. Independent associations with BCR were identified for the PSA level before SRT (RR [doubling]: 1.25, P < 0.001), pathological tumour stage (RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score (RR [7 vs <7] 1.63, P < 0.001; RR [8-10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status (RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c-index of 0.66. Scores ranged from 0 to 7, and 5-year freedom from BCR for different levels of the score was as follows: Score = 0-1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5-7: 15%. CONCLUSION: We developed a scoring system that provides an estimation of the risk of BCR after SRT. These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting.

Compliance with National Comprehensive Cancer Network guidelines in the use of radiation therapy for extremity and superficial trunk soft tissue sarcoma in the United States.

BACKGROUND: We sought to examine adherence to National Comprehensive Cancer Network guidelines for use of radiation therapy (RT) in patients with soft tissue sarcoma (STS) in the United States. METHODS: The surveillance, epidemiology, and end results cancer registry was queried to identify patients undergoing surgery for truncal and extremity STS from 2004 to 2009. RESULTS: Of 5,075 patients, 50% received RT. Although routine RT is not recommended for Stage I patients, 25% still underwent RT. Even though routine RT is recommended for Stage II and III tumors, only 60% underwent RT. On multivariate analysis predictors of RT included age <50 years (OR 1.57, 95% CI 1.28-1.91), malignant fibrous histiocytoma histology (OR 1.47, 95% CI 1.3-1.92), T2 classification (OR 1.88, 95% CI 1.60-2.20), and G3 (OR 6.27, 95% CI 5.10-7.72). Patients with Stage III STS who received RT showed improved disease specific survival at 5 years compared to those who did not, 68% versus 46%, P <0.001. CONCLUSIONS: Underuse of RT is seen for a significant proportion of patients undergoing treatment for STS in the United States. More effort needs to be directed towards compliance with appropriate treatment recommendations, perhaps by regionalizing sarcoma care or remote multidisciplinary tumor boards.

Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity.

Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45cm(3) of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.

Extranodal rosai-dorfman disease of the bone treated with surgery and radiotherapy.

Rosai-Dorfman disease (RDD) is a rare, benign histiocyte disorder originally described by Rosai and Dorfman in 1969 as sinus histiocytosis with massive lymphadenopathy. It most typically presents as massive, painless cervical lymphadenopathy, and it is most often found in adolescents and young adults. Extranodal involvement is a common feature of RDD and may occur in more than 40% of patients. Less commonly, the disease can be seen in the bone. There are scattered case reports discussing the use of radiotherapy in the treatment of RDD. Here, we present a case of extranodal RDD of the femur in a 49-year-old African American female. The patient underwent three surgical procedures prior to undergoing radiotherapy. Pathology was consistent with extranodal RDD. The cells stained positive for CD68 and S-100. Pathognomonic features such as emperipolesis and replacement of the bone marrow by diffuse infiltrating of histiocytes and intervening bands of plasma cells proliferation were noted. Prior to radiotherapy, the patient required a walker to assist with ambulation and was utilizing a wheelchair while in the clinic. The decision was made to proceed with 30 Gy of external beam radiotherapy in 15 fractions. After five fractions, the patient's pain resolved entirely. She no longer required pain medication and was ambulating without assistance. She experienced no adverse events from the radiation. Extranodal RDD is a rare disorder, and evidence for treatment is derived from scattered case reports. Previous reports have indicated a dose response to radiotherapy in the 20-30 Gy range for RDD; however, our patient developed complete resolution of her symptoms after 10 Gy. While the optimal dose regimen has not yet been established, symptomatic patients appear to benefit from external beam radiotherapy for extranodal RDD.

Lack of Association between COX-2 Staining Level and Biochemical Recurrence Following Salvage Radiation Therapy for Recurrent Prostate Cancer.

OBJECTIVE: The ability to predict which men will experience biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer following radical prostatectomy has potential for improvement. Cyclooxygenase-2 (COX-2) overexpression has previously correlated with poor clinical outcomes following primary treatment for prostate cancer, however its predictive ability in the specific setting of SRT has not been examined to date. This study evaluated the association between COX-2 staining intensity and BCR following SRT for recurrent prostate cancer. METHODS: We utilized a cohort of 151 patients who underwent SRT between July 1987 and July 2003. COX-2 staining intensity in primary tumor samples was detected using monoclonal antibodies and quantified using a computer-assisted method. The association between COX-2 staining intensity and BCR was evaluated using multivariable Cox regression models. RESULTS: When examining COX-2 staining level as three-level categorical variable (low, moderate, high) based on approximate sample tertiles, there was no evidence of an association with BCR (P=0.18). More specifically, in comparison to patients with low staining intensity, there was no significant difference in risk of BCR for moderate (Relative risk [RR]: 1.17, P=0.56) or high (RR: 0.72, P=0.22) COX-2 staining intensity patients. This lack of association was also observed when considering COX-2 staining intensity as a continuous variable (RR: 0.83, P=0.15). CONCLUSION: Our results indicate that COX-2 staining intensity is likely of little use in discriminating prognosis of SRT. It appears that the search for prognostic factors associated with BCR should continue elsewhere in order to further enhance patient selection for SRT.

Complications after 90Y microsphere radioembolization for unresectable hepatic tumors: An evaluation of 112 patients.

PURPOSE: The aim of this study was to estimate the incidence of complications after (90)Y microsphere radioembolization for unresectable hepatic tumors and evaluate risk factors for late complications. METHODS AND MATERIALS: A cohort of 112 consecutive patients from two institutions underwent (90)Y microsphere radioembolization for unresectable hepatic tumors. Complications were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Symptoms secondary to postradioembolization syndrome occurring within 30 days were recorded as early complications, and all other complications were considered late complications. RESULTS: Seventy-eight patients (70%) experienced postradioembolization syndrome, including fatigue, abdominal pain, nausea, vomiting, anorexia, or fever. Three patients (3%) experienced a Grade 3 early complication; no Grade 4 or 5 early toxicity occurred. Two patients (2%) experienced clinically significant liver dysfunction; 13 patients (12%), 27 patients (24%), and 9 patients (8%) had an elevation of bilirubin, aspartate aminotransferase, and alanine aminotransferase, respectively. Eleven patients (10%) experienced gastrointestinal ulceration, including two Grade 3 complications and one Grade 4 complication. Cholecystitis occurred in 7 patients (6%), including two Grade 3 complications. Grade 2 pancreatitis occurred in 1 patient (1%). No radiation pneumonitis was observed. The cumulative incidence of late Grade 3 or 4 complications at 12 months after radioembolization was 8%. No Grade 5 toxicity occurred. CONCLUSIONS: (90)Y microsphere radioembolization is a well-tolerated treatment for unresectable hepatic tumors with a low risk of Grade 3 or higher early or late toxicity.

Oropharyngeal squamous cell carcinoma metastatic to lower-extremity soft tissues: a case report and literature review.

A 52-year old man was referred to our service for evaluation after being diagnosed with oropharyngeal squamous cell carcinoma. Contrast-enhanced computed tomography (CT) revealed a mass in the left tonsillar pillar, as well as submental lymphadenopathy. The extent of tumor infiltration was assessed by fluoro-2-deoxyglucose positron emission tomography scans, which showed increased uptake in the tumor bed and a suspicious-looking lymph node near the right hilum. No other signs or symptoms of distant metastasis were evident at that time, and the patient was treated with induction chemotherapy followed by chemoradiation. Several weeks after treatment completion, the patient returned, complaining of right medial foot edema. CT of the right lower extremity revealed multiple high-attenuation masses in the soft tissues of the right leg and foot, including a mass in the medial plantar region of the foot. Approximately 15 to 20% of patients with oropharyngeal squamous cell carcinoma develop distant metastasis throughout the course of the disease. Soft-tissue metastases from oropharyngeal cancers are rare, however, particularly when they present in the absence of widespread metastasis. A review of the current head and neck tumor literature describes soft-tissue metastases in less than 10% of patients with known distant metastases. Metastasis to distal regions such as the lower extremities has rarely been observed but should be included in the differential diagnosis for patients presenting with lower-extremity pain or edema.

Evaluation of Serum Calcium as a Predictor of Biochemical Recurrence following Salvage Radiation Therapy for Prostate Cancer.

Background. Previous reports have shown a positive association between serum calcium level and prostate cancer mortality. However, there is no data regarding whether higher serum calcium levels are associated with increased risk of biochemical recurrence (BCR) following salvage radiation therapy (SRT) for prostate cancer. Herein, we evaluate the association between pretreatment serum calcium levels and BCR in a cohort of men who underwent SRT. Methods. We evaluated 165 patients who underwent SRT at our institution. Median dose was 65.0 Gy (range: 54.0-72.4 Gy). We considered serum calcium as both a continuous variable and a 3-level categorical variable (low [≤9.0 mg/dL], moderate [>9.0 mg/dL and ≤9.35 mg/dL], and high [>9.35 mg/dL]) based on sample tertiles. Results. We observed no evidence of a linear association between serum calcium and BCR (relative risk (RR): 0.96, P = 0.76). Compared to men with low calcium, there was no significantly increased risk of BCR for men with moderate (RR: 0.94, P = 0.79) or high (RR: 1.08, P = 0.76) serum calcium levels. Adjustment for clinical, pathological, and SRT characteristics in multivariable analyses did not alter these findings. Conclusion. Our results provide evidence that pretreatment serum calcium is unlikely to be a useful tool in predicting BCR risk following SRT.

Tumor bed-to-skin distance using accelerated partial-breast irradiation with the strut-adjusted volume implant device.

PURPOSE: Because of the risk of skin toxicity with single dwell position, single-lumen brachytherapy devices are sometimes contraindicated for tumor cavities 5-7mm from the skin surface. We discuss the use of multicatheter device to treat patients with tumor bed-to-skin distances <7mm. METHODS AND MATERIALS: We treated 117 patients with accelerated partial-breast irradiation brachytherapy: 77 single-lumen and 40 multicatheter devices. A subset of 12 patients treated with SAVI(®) had bed-to-skin spacing <7mm. All patients had Tis-2N0 ductal carcinoma with negative margins. A total dose of 34.0Gy in 10 fractions was delivered twice daily. Planning target volume was created using computed tomography-based three-dimensional planning with a 1.0-cm expansion of the lumpectomy cavity. Skin dose was measured dosimetrically, with skin constraints <125% of the prescription. Toxicities were graded, and patients were assessed at various intervals. RESULTS: Of the patients treated with the multicatheter device, 0% (0/12) had their device pulled. At 2 weeks after treatment, fewer than 50% of the patients had skin toxicities of Grades 1-2, all of which resolved by 6 months. The cosmetic outcome was good to excellent at followup. CONCLUSIONS: Multicatheter devices permit well-tolerated accelerated partial-breast irradiation in patients with tumor cavities near the skin surface for which the single-lumen device may not be appropriate.

Polyglutamine repeat length-dependent proteolysis of huntingtin.

Amino-terminal fragments of huntingtin, which contain the expanded polyglutamine repeat, have been proposed to contribute to the pathology of Huntington's disease (HD). Data supporting this claim have been generated from patients with HD in which truncated amino-terminal fragments forming intranuclear inclusions have been observed, and from animal and cell-based models of HD where it has been demonstrated that truncated polyglutamine-containing fragments of htt are more toxic than full-length huntingtin. We report here the identification of a region within huntingtin, spanning from amino acids 63 to 111, that is cleaved in cultured cells to generate a fragment of similar size to those observed in patients with HD. Importantly, proteolytic cleavage within this region appears dependent upon the length of the polyglutamine repeat within huntingtin, with pathological polyglutamine repeat-containing huntingtin being more efficiently cleaved than huntingtin containing polyglutamine repeats of nonpathological size.