Ryan J. Burri

Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

PURPOSE To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. METHODS AND MATERIALS Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with (103)Pd or (125)I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. RESULTS Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade > or = 2 toxicity (p = 0.03). CONCLUSION With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

Association of Single Nucleotide Polymorphisms in SOD2, XRCC1 and XRCC3 with Susceptibility for the Development of Adverse Effects Resulting from Radiotherapy for Prostate Cancer

Abstract Burri, R. J., Stock, R. G., Cesaretti, J. A., Atencio, D. P., Peters, S., Peters, C. A., Fan, G., Stone, N. N., Ostrer, H. and Rosenstein, B. S. Association of Single Nucleotide Polymorphisms in SOD2, XRCC1 and XRCC3 with Susceptibility for the Development of Adverse Effects Resulting from Radiotherapy for Prostate Cancer. Radiat. Res. 170, 49–59 (2008). The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P = 0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P = 0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P = 0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.

Radiation dose predicts for biochemical control in intermediate-risk prostate cancer patients treated with low-dose-rate brachytherapy.

PURPOSE To evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (FFbF) in patients with intermediate-risk prostate cancer. METHODS AND MATERIALS From a prospectively collected database of 2250 men treated at Mount Sinai Hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen [PSA] level 10-20 ng/mL, Gleason score 7, or Stage T2b) were identified who had a minimum follow-up of 24 months and postimplant CT-based dosimetric analysis. Biologically effective dose (BED) values were calculated to compare doses from different isotopes and treatment regimens. Patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. Patient- and treatment-related factors were analyzed with respect to FFbF. The median follow-up was 60 months (range, 24-167 months). Biochemical failure was defined according to the Phoenix definition. Univariate analyses were used to determine whether any variable was predictive of FFbF. A two-sided p value of <0.05 was considered significant. RESULTS Overall, the actuarial FFbF at 10 years was 86%. Dose (BED <150 Gy(2) vs. >or=150 Gy(2)) was the only significant predictor of FFbF (p < 0.001). None of the other variables (PSA, external-beam radiotherapy, Gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year FFbF. CONCLUSIONS Radiation dose is an important predictor of FFbF in intermediate-risk prostate cancer. Treatment should continue to be individualized according to presenting disease characteristics until results from Radiation Therapy Oncology Group trial 0232 become available.

Correlation of Positron Emission Tomography Standard Uptake Value and Pathologic Specimen Size in Cancer of the Head and Neck

PURPOSE To correlate positron emission tomography (PET) standard uptake value (SUV) with pathologic specimen size in patients with head-and-neck cancers. METHODS AND MATERIALS Eighteen patients with Stage II-IVB head-and-neck cancer with 27 tumors who underwent PET and computed tomography (CT) imaging of the head and neck followed by surgical resection were selected for this study. Various SUV thresholds were examined, including the software default (SUV(def)), narrowing the window by 1 standard deviation (SD) of the maximum (SUV-1SD), and SUV cutoff values of 2.5 or greater (SUV2.5) and 40% or greater maximum (SUV40). Volumetric pathologic data were available for 12 patients. Tumor volumes based on pathologic examination (gold standard), CT, SUV(def), SUV-1SD, SUV2.5, and SUV40 were analyzed. RESULTS PET identified five tumors not seen on CT. The sensitivity of PET for identifying primary tumors was 94% (17 of 18). The Sensitivity of PET for staging the neck was 90% (9 of 10), whereas the specificity was 78% (7 of 9). The SUV2.5 method was most likely to overestimate tumor volume, whereas SUV(def) and SUV-1SD were most likely to underestimate tumor volume. CONCLUSIONS The PET scan provides more accurate staging of primary tumors and nodal metastases for patients with advanced head-and-neck cancer than CT alone. Compared with the gold standard, significant variability exists in volumes obtained by using various SUV thresholds. A combination of clinical, CT, and PET data should continue to be used for optimal treatment planning. The SUV40 method appears to offer the best compromise between accuracy and reducing the risk of underestimating tumor extent.

YOUNG MEN HAVE EQUIVALENT BIOCHEMICAL OUTCOMES COMPARED WITH OLDER MEN AFTER TREATMENT WITH BRACHYTHERAPY FOR PROSTATE CANCER

PURPOSE To evaluate retrospectively the biochemical outcomes of young men treated with low-dose-rate brachytherapy for prostate cancer. METHODS AND MATERIALS From 1990 to 2005, 1,665 men with clinically localized prostate cancer were treated with low-dose-rate brachytherapy +/- hormone therapy (HT) +/- external beam radiotherapy and underwent > or = 2 years of follow-up. Patients were stratified on the basis of age: < or = 60 (n = 378) and >60 years (n = 1,287). Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine the association of variables with freedom from biochemical failure (FFbF). RESULTS Median follow-up was 68 months (range, 24-180) for men < or = 60 years and 66 months (range, 24-200) for men >60. For the entire group, the actuarial 5- and 8-year FFbF rates were 94% and 88%, respectively. Men < or = 60 demonstrated similar 5- and 8-year FFbF (95% and 92%) compared with men >60 (93% and 87%; p = 0.071). A larger percent of young patients presented with low-risk disease; lower clinical stage, Gleason score (GS), and pretreatment PSA values; were treated after 1997; did not receive any HT; and had a high biologic effective dose (BED) of radiation (all ps <0.001). On multivariate analysis, PSA (p = 0.001), GS (p = 0.005), and BED (p < 0.001) were significantly associated with FFbF, but age was not (p = 0.665). CONCLUSION Young men achieve excellent 5- and 8-year biochemical control rates that are comparable to those of older men after prostate brachytherapy. Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer.

Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer

The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated‐boost (SIB), intensity‐modulated radiation therapy (IMRT) into a well described 5‐fluorouracil (5‐FU) and hydroxyurea (HU)‐based chemoradiation regimen.

Concurrent chemotherapy and radiotherapy for head and neck cancer

Head and neck cancer is best managed in a multidisciplinary setting. Surgery, radiation therapy, chemotherapy and, more recently, biologic therapy are often employed in various combinations in an attempt to eradicate both clinically apparent and occult disease. The goals of treatment include maximizing tumor control while maintaining function and quality of life. Most patients present with locally advanced disease, and multimodality organ-conserving therapy is often employed for these patients based on the results of multiple Phase III clinical trials. This article focuses on the rationale and evidence supporting the use of concurrent chemotherapy and radiation therapy in the management of locally advanced head and neck cancers.