Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial.

We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1-84.5) and 65% (95% CI: 52.5-76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0-80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6-83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence.

MRI-LINAC: A transformative technology in radiation oncology.

Advances in radiotherapy technologies have enabled more precise target guidance, improved treatment verification, and greater control and versatility in radiation delivery. Amongst the recent novel technologies, Magnetic Resonance Imaging (MRI) guided radiotherapy (MRgRT) may hold the greatest potential to improve the therapeutic gains of image-guided delivery of radiation dose. The ability of the MRI linear accelerator (LINAC) to image tumors and organs with on-table MRI, to manage organ motion and dose delivery in real-time, and to adapt the radiotherapy plan on the day of treatment while the patient is on the table are major advances relative to current conventional radiation treatments. These advanced techniques demand efficient coordination and communication between members of the treatment team. MRgRT could fundamentally transform the radiotherapy delivery process within radiation oncology centers through the reorganization of the patient and treatment team workflow process. However, the MRgRT technology currently is limited by accessibility due to the cost of capital investment and the time and personnel allocation needed for each fractional treatment and the unclear clinical benefit compared to conventional radiotherapy platforms. As the technology evolves and becomes more widely available, we present the case that MRgRT has the potential to become a widely utilized treatment platform and transform the radiation oncology treatment process just as earlier disruptive radiation therapy technologies have done.

Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial.

BACKGROUND: Previous phase 2 trials of neoadjuvant anti-PD-1 or anti-PD-L1 monotherapy in patients with early-stage non-small-cell lung cancer have reported major pathological response rates in the range of 15-45%. Evidence suggests that stereotactic body radiotherapy might be a potent immunomodulator in advanced non-small-cell lung cancer (NSCLC). In this trial, we aimed to evaluate the use of stereotactic body radiotherapy in patients with early-stage NSCLC as an immunomodulator to enhance the anti-tumour immune response associated with the anti-PD-L1 antibody durvalumab. METHODS: We did a single-centre, open-label, randomised, controlled, phase 2 trial, comparing neoadjuvant durvalumab alone with neoadjuvant durvalumab plus stereotactic radiotherapy in patients with early-stage NSCLC, at NewYork-Presbyterian and Weill Cornell Medical Center (New York, NY, USA). We enrolled patients with potentially resectable early-stage NSCLC (clinical stages I-IIIA as per the 7th edition of the American Joint Committee on Cancer) who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were randomly assigned (1:1) to either neoadjuvant durvalumab monotherapy or neoadjuvant durvalumab plus stereotactic body radiotherapy (8 Gy × 3 fractions), using permuted blocks with varied sizes and no stratification for clinical or molecular variables. Patients, treating physicians, and all study personnel were unmasked to treatment assignment after all patients were randomly assigned. All patients received two cycles of durvalumab 3 weeks apart at a dose of 1·12 g by intravenous infusion over 60 min. Those in the durvalumab plus radiotherapy group also received three consecutive daily fractions of 8 Gy stereotactic body radiotherapy delivered to the primary tumour immediately before the first cycle of durvalumab. Patients without systemic disease progression proceeded to surgical resection. The primary endpoint was major pathological response in the primary tumour. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrial.gov, NCT02904954, and is ongoing but closed to accrual. FINDINGS: Between Jan 25, 2017, and Sept 15, 2020, 96 patients were screened and 60 were enrolled and randomly assigned to either the durvalumab monotherapy group (n=30) or the durvalumab plus radiotherapy group (n=30). 26 (87%) of 30 patients in each group had their tumours surgically resected. Major pathological response was observed in two (6·7% [95% CI 0·8-22·1]) of 30 patients in the durvalumab monotherapy group and 16 (53·3% [34·3-71·7]) of 30 patients in the durvalumab plus radiotherapy group. The difference in the major pathological response rates between both groups was significant (crude odds ratio 16·0 [95% CI 3·2-79·6]; p<0·0001). In the 16 patients in the dual therapy group with a major pathological response, eight (50%) had a complete pathological response. The second cycle of durvalumab was withheld in three (10%) of 30 patients in the dual therapy group due to immune-related adverse events (grade 3 hepatitis, grade 2 pancreatitis, and grade 3 fatigue and thrombocytopaenia). Grade 3-4 adverse events occurred in five (17%) of 30 patients in the durvalumab monotherapy group and six (20%) of 30 patients in the durvalumab plus radiotherapy group. The most frequent grade 3-4 events were hyponatraemia (three [10%] patients in the durvalumab monotherapy group) and hyperlipasaemia (three [10%] patients in the durvalumab plus radiotherapy group). Two patients in each group had serious adverse events (pulmonary embolism [n=1] and stroke [n=1] in the durvalumab monotherapy group, and pancreatitis [n=1] and fatigue [n=1] in the durvalumab plus radiotherapy group). No treatment-related deaths or deaths within 30 days of surgery were reported. INTERPRETATION: Neoadjuvant durvalumab combined with stereotactic body radiotherapy is well tolerated, safe, and associated with a high major pathological response rate. This neoadjuvant strategy should be validated in a larger trial. FUNDING: AstraZeneca.

Glamour, expression, and consequences of tattoos in radiation treatment.

It is estimated that approximately 24% of the US population has at least one tattoo. However, tattoo ink ingredients include heavy metals (high atomic number Z) that are not regulated, which can cause skin reactions. This study investigates the dosimetric effects in surface dose due to high-Z elements in tattoo ink under electron beam irradiation. Four commercially available tattoo ink colors, black, red, yellow, and blue were chosen. The elemental composition of the tattoo ink samples was analyzed using X-ray Fluorescence (XRF). An ultrathin-window parallel plate ion chamber was used to measure the surface dose perturbation (ratio of ionizations with and without tattoo ink) for 6 - 20 MeV electron beams. The elemental concentration in the tattoo ink samples showed high-Z elements, with Z ranging from 11 to 92. The dose perturbation ranged from 1.4% up to 6% for the yellow ink for the 6 MeV electron beam, with similar values across the rest of the electron energies, whereas the black, red, and blue inks presented up to 3% dose perturbation for the same range of energies. Based on this initial study, we conclude that commercially available tattoo inks contain large amounts of high-Z metals that may contribute to dose perturbation. Therefore treatment of superficial lesions with electron beams in a tattooed area should be monitored for signs of early skin reaction during radiation therapy treatments.

Dosimetric assessment of tumor control probability in intensity and volumetric modulated radiotherapy plans.

OBJECTIVE:: Radiobiological models have been used to calculate the outcomes of treatment plans based on dose-volume relationship. This study examines several radiobiological models for the calculation of tumor control probability (TCP) of intensity modulated radiotherapy plans for the treatment of lung, prostate, and head and neck (H&N) cancers. METHODS:: Dose volume histogram (DVH) data from the intensity modulated radiotherapy plans of 36 lung, 26 prostate, and 87 H&N cases were evaluated. The Poisson, Niemierko, and Marsden models were used to calculate the TCP of each disease group treatment plan. The calculated results were analyzed for correlation and discrepancy among the three models, as well as different treatment sites under study. RESULTS:: The median value of calculated TCP in lung plans was 61.9% (34.1-76.5%), 59.5% (33.5-73.9%) and 32.5% (0.0-93.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in prostate plans was 85.1% (56.4-90.9%), 81.2% (56.1-88.7%) and 62.5% (28.2-75.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in H&N plans was 94.0% (44.0-97.8%) and 94.3% (0.0-97.8%) with the Poisson and Niemierko models, respectively. There were significant differences between the calculated TCPs with the Marsden model in comparison with either the Poisson or Niemierko model (p < 0.001) for both lung and prostate plans. The TCPs calculated by the Poisson and Niemierko models were significantly correlated for all three tumor sites. CONCLUSION:: There are variations with different radiobiological models. Understanding of the correlation and limitation of a TCP model with dosimetric parameters can help develop the meaningful objective functions for plan optimization, which would lead to the implementation of outcome-based planning. More clinical data are needed to refine and consolidate the model for accuracy and robustness. ADVANCES IN KNOWLEDGE:: This study has tested three radiobiological models with varied disease sites. It is significant to compare different models with the same data set for better understanding of their clinical applicability.

HIV Infection Is Associated With Poor Outcomes for Patients With Anal Cancer in the Highly Active Antiretroviral Therapy Era.

BACKGROUND: HIV status may affect outcomes after definitive chemoradiotherapy for anal cancer. OBJECTIVE: Here, we report a large series in the highly active antiretroviral therapy era comparing outcomes between HIV-positive and HIV-negative patients with anal cancer. DESIGN: This was a retrospective chart review. SETTINGS: The study was conducted at an outpatient oncology clinic at large academic center. PATIENTS: A total of 107 patients were reviewed, 39 HIV positive and 68 HIV negative. All of the patients underwent definitive chemoradiation for anal cancer. MAIN OUTCOME MEASURES: Data on patient characteristics, treatment, toxicity, and outcomes were collected. Overall survival, colostomy-free survival, local recurrence-free survival, and distant metastasis-free survival were analyzed. RESULTS: Median follow-up was 15 months. HIV-positive patients were younger (median, 52 vs 64 years; p < 0.001) and predominantly men (82% men vs 49% men; p = 0.001). There were no significant differences in T, N, or stage groups. HIV-positive patients had a significantly longer duration from biopsy to start of chemoradiation (mean number of days, 82 vs 54; p = 0.042). There were no differences in rates of acute toxicities including diarrhea, fatigue, or dermatitis. HIV-positive patients had significantly higher rates of hospitalization (33% vs 15%; p = 0.024). The 3-year overall survival rate was 42% in HIV-positive and 76% in HIV-negative patients (p = 0.037; HR, 2.335 (95% CI, 1.032-5.283)). Three-year colostomy-free survival was 67% in HIV-positive and 88% in HIV-negative patients (p = 0.036; HR, 3.231 (95% CI, 1.014-10.299)). Differences in overall survival rates were not significant on multivariate analysis. LIMITATIONS: This study was limited by its retrospective design and small patient numbers. CONCLUSIONS: In this cohort, HIV-positive patients had significantly worse overall and colostomy-free survival rates than HIV-negative patients. However, differences in survival were not significant on multivariate analysis. Additional studies are necessary to establish the etiology of this difference.

Comparison of anal cancer outcomes in public and private hospital patients treated at a single radiation oncology center.

OBJECTIVE: To compare clinical and treatment characteristics and outcomes in locally advanced anal cancer, a potentially curable disease, in patients referred from a public or private hospital. METHODS: We retrospectively reviewed 112 anal cancer patients from a public and a private hospital who received definitive chemoradiotherapy at the same cancer center between 2004 and 2013. Tumor stage, radiotherapy delay, radiotherapy duration, and unplanned treatment breaks ≥10 days were compared using t-test and χ(2) test. Overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS) were examined using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard models for OS and DFS were developed. RESULTS: The follow-up was 14.9 months (range, 0.7-94.8 months). Public hospital patients presented with significantly higher clinical T stage (P<0.05) and clinical stage group (P<0.05), had significantly longer radiotherapy delays (P<0.05) and radiotherapy duration (P<0.05), and had more frequent radiation therapy (RT) breaks ≥10 days (P<0.05). Three-year OS showed a marked trend in favor of private hospital patients for 3-year OS (72.8% vs. 48.9%; P=0.171), 3-year DFS (66.3% vs. 42.7%, P=0.352), and 3-year CFS (86.4% vs. 68.9%, P=0.299). Referral hospital was not predictive of OS or DFS on multivariate analysis. CONCLUSIONS: Public hospital patients presented at later stage and experienced more delays in initiating and completing radiotherapy, which may contribute to the trend in poorer DFS and OS. These findings emphasize the need for identifying clinical and treatment factors that contribute to decreased survival in low socioeconomic status (SES) populations.

Concurrent chemoradiation for high-risk prostate cancer.

There are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. There is a subset of patients that are likely to recur after locoregional treatment that is thought of as a "high-risk" population. This more aggressive subset includes patients with clinical stage greater than T2b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/dL. The rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. These trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. This review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.

Predictors of Complete Response and Disease Recurrence Following Chemoradiation for Rectal Cancer.

OBJECTIVE: Approximately 10-40% of rectal patients have a complete response (CR) to neoadjuvant chemoradiation (CRT), and these patients have improved survival. Thus, non-operative management ("watch-and-wait" approach) may be an option for select patients. We aimed to identify clinical predictors of CR following CRT. METHODS: Patients treated with definitive CRT for T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal cancer from August 2004 to February 2015 were retrospectively reviewed. Most patients were treated with 50.4 Gy radiation and concurrent 5-fluoruracil or capecitabine. Patients were considered to have a CR if surgical pathology revealed ypT0N0M0 (operative management), or if they had no evidence of residual disease on clinical and radiographic assessment (non-operative management). Statistical analysis was carried out to determine predictors of CR and long-term outcomes. RESULTS: Complete records were available on 138 patients. The median follow-up was 24.5 months. Thirty-six patients (26.3%) achieved a CR; 30/123 operatively managed patients (24.5%) and 6/15 (40%) non-operatively managed patients. None of the 10 patients with mucinous adenocarcinoma achieved a CR. Carcinoembryonic antigen (CEA) ≥5 µg/L at diagnosis (OR 0.190, 95% CI 0.037-0.971, p = 0.046), tumor size ≥3 cm (OR 0.123, 95% CI 0.020-0.745, p = 0.023), distance of tumor from the anal verge ≥3 cm (OR 0.091, 95% CI 0.013-0.613, p = 0.014), clinically node-positive disease at diagnosis (OR 0.201, 95% CI 0.045-0.895, p = 0.035), and interval from CRT to surgery ≥8 weeks (OR 5.267, 95% CI 1.068-25.961, p = 0.041) were independent predictors of CR. The CR group had longer 3-year distant metastasis-free survival (DMFS) (93.7 vs. 63.7%, p = 0.016) and 3-year disease-free survival (DFS) (91.1 vs. 67.8%, p = 0.038). Three-year locoregional control (LRC) (96.6 vs. 81.3%, p = 0.103) and overall survival (97.2 vs. 87.5%, p = 0.125) were higher in the CR group but this did not achieve statistical significance. CR was not an independent predictor of LRC, DMFS, or DFS. CONCLUSION: CEA at diagnosis, tumor size, tumor distance from the anal verge, node positivity at diagnosis, and interval from CRT to surgery were predictors of CR. These clinical variables may offer insight into patient selection and timing of treatment response evaluation in the watch-and-wait approach.

Toxicity and disease-related outcomes after radiotherapy for head and neck cancer in human immunodeficiency virus-positive patients.

BACKGROUND: Human immunodeficiency virus (HIV) seropositivity may be associated with higher risk of local recurrence and poor survival in multiple malignancies. However, long-term disease control in HIV-positive patients with head and neck cancer (HNC) is not well described. The purpose of this study is to review the disease-related outcomes of HIV-positive patients who underwent radiotherapy (RT) or chemoradiotherapy (CRT) at our institution. METHODS: We retrospectively reviewed 24 HIV-positive patients who underwent RT for HNC between 2004 and 2013. Patient characteristics, treatment details, and outcomes were collected. Overall survival (OS) and local recurrence-free survival (LRFS) were investigated. Kaplan-Meier estimated survival was calculated. RESULTS: Median follow-up was 21 months. All patients were treated with curative intent. Eighty-three percent had stage III-IV. Primary sites of disease included oropharynx (n = 12), larynx (n = 6), oral cavity (n = 2), unknown primary (n = 2), nasal cavity (n = 1), and paranasal sinuses (n = 1). Four patients (17%) had definitive RT alone and nine had definitive CRT (38%; eight cisplatin and one cetuximab). Eleven (46%) were treated in the adjuvant setting after surgical resection; six with RT alone and five with concurrent cisplatin. Eight patients had acute Grade 3 toxicity with no acute Grade 4 or 5 toxicities. Fifteen patients (63%) were alive and disease-free. Two- and 5-year OS was 67 and 59%, respectively. LRFS at 2-years was 82%. Median OS was 83 months. CONCLUSION: In this cohort, HIV-positive patients treated aggressively with curative intent had excellent OS and local control following RT or CRT for HNC compared to historical controls. Treatment was relatively well tolerated. This group of patients should be managed aggressively with intent to cure.

Novel use of endoscopically placed fiducial markers for targeted radiation therapy of colonic lymphomas.

Non-Hodgkin's lymphomas (NHL) are an important variety of gastrointestinal tumors with increasing incidence and prevalence. Traditional management of NHL with chemotherapy is challenging and expanding evidence points to significant tumor response to radiation therapy (RT). However, there exists a wide range of radiation-related toxicities. Optimization of exact tumor marking coupled with minimization of the radius of radiation delivery is essential to increase patient's tolerance and decrease side effects of the treatment. We report our experience with mantle cell lymphoma of the colon treated with precision RT after endoscopic placement of resolution clips in a "shooting target" fashion in a patient who failed conventional chemotherapy. Fourteen months after completion of RT, the patient remains in complete remission.

Feasibility and efficacy of local radiotherapy with concurrent novel agents in patients with multiple myeloma.

INTRODUCTION: This study evaluated the safety and efficacy of radiotherapy (RT) with concurrent novel agents (NAs), cytotoxic therapy (CTx), or both in the management of osteolytic bone lesions in multiple myeloma (MM). PATIENTS AND METHODS: A total of 39 patients with MM received RT to 64 different bone sites during the 2007-2012 period, with a dose of 8 to 37.5 Gy (mean, 26.8 Gy) delivered in 1 to 15 fractions (median, 10 fractions). Of these patients, 21 also received concurrent NAs or CTx. Pain response, M protein and κ light chain response, and adverse events were evaluated. RESULTS: RT was completed in 35 of 39 patients (89.7%) in this study. Pain relief was observed in 30 of 31 patients (96.7%). Hematologic toxicity (grade 3 or 4 by the Radiation Therapy Oncology Group system) was seen in 43.2% of treated patients, and NA therapy was stopped in 2 patients owing to grade 4 toxicity. RT adverse effects resolved at 4 to 6 weeks posttreatment. Changes in pre- and posttreatment levels of M protein trended toward significance in patients treated with RT + systemic therapy (ST) versus. RT alone (ΔM ProteinRT+ST = 5.6 g/L; ΔM ProteinRT = 0 g/L; P = .089). CONCLUSION: Treating MM with RT concurrently with CTx including NAs was safe and well tolerated in the majority of patients (14 of 16 [87.5%] for those taking NAs and 19 of 21 [90.5%] for all patients). Excellent clinical pain response (> 95%) was also seen in patients regardless if they were treated with RT + ST or RT alone.

Hypofractionated radiation therapy for prostate cancer: biologic and technical considerations.

The optimal radiation schedule for the curative treatment of prostate cancer is not known. The dose-response of tumors and normal tissues to fractionated irradiation can be described according to a parameter called the alpha-beta ratio (α/ß). In the past several years numerous reports have been published that suggest that the alpha-beta ratio for prostate cancer may be quite low; between 1 and 3. If this hypothesis is true, then a radiation therapy schedule that employs less frequent and larger fractions, termed hypofractionation, may be more efficacious. Multiple randomized trials have been conducted comparing moderate (less than 5 Gy/day) hypofractionated radiation therapy and standard radiation therapy in men with prostate cancer. In the majority of these studies the moderate hypofractionated arm had equivalent efficacy with a similar or improved side effect profile. One area to use caution may be in patients with compromised (IPSS > 12) urinary function at baseline due to an increase in urinary toxicity observed in patients treated with hypofractionated radiation in one study. Extreme hypofractionation (greater than or equal to 5 Gy/day), is currently being compared in a randomized trial. Early prospectively collected data from multiple institutions demonstrates efficacy and toxicity that compares favorably with historical controls. The cost savings from hypofractionation could be profound on a national level and only increases the necessity of testing hypofractionated treatment schedules. Long term data and future trials will help radiation oncologists determine the ideal fractionation scheme based on cost, efficacy, and toxicity.

Management of high-risk localized prostate cancer.

Traditionally, patients with high-risk localized prostate cancer have been an extremely challenging group to manage due to a significant likelihood of treatment failure and prostate cancer-specific mortality (PCSM). The results of multiple large, prospective, randomized trials have demonstrated that men with high-risk features who are treated in a multimodal fashion at the time of initial diagnosis have improved overall survival. Advances in local treatments such as dose-escalated radiotherapy in conjunction with androgen suppression and postprostatectomy adjuvant radiotherapy have also demonstrated benefits to this subset of patients. However, therapeutic enhancement with the addition of chemotherapy to the primary treatment regimen may help achieve optimal disease control.

Squamous cell carcinoma of the prostate.

Squamous cell carcinoma of the prostate is a rare tumor, making up 0.5% to 1% of all prostate carcinomas. It is typically described as an aggressive cancer, with a median postdiagnosis survival of 14 months. Presented here is a case of primary squamous cell carcinoma of the prostate, with a complicated presentation of metastatic disease. Due to the extent of the patient's disease, he was treated with palliative radiation therapy using a four-field technique (AP/PA and left and right lateral fields) with 18 mV photons prescribed to the 100% isodose line. The prescription dose was 4000 cGy in 16 fractions of 250 cGy per fraction. No definitive treatment of squamous cell carcinoma of the prostate exists but varying approaches including surgical intervention, chemotherapy, and radiation therapy have been implemented without durable response. However, multimodal treatments appear to be the most promising with longer durations of survival.

Review of chemoradiotherapy for high-risk prostate cancer.

While most newly-diagnosed prostate cancers are well-differentiated tumors that have high probability of cure, there is a subset of patients that present with aggressive malignancies that have significant potential for recurrence and metastasis. Single-modality treatment approaches have demonstrated relatively high failure rates, and multimodality therapy (radiation therapy and hormonal ablation therapy) has become standard of care for these patients. These treatments are not without toxicity, and a significant percentage of patients will become refractory to hormonal therapy. Historically, radiation therapy of prostate cancer was associated with significant genitourinary and gastrointestinal morbidity. With advances in radiation therapy techniques and delivery, the potential for safe dose-escalation has emerged. Further, there is an opportunity for chemotherapeutic agents to play an important syngergistic role in radiosensitizing the tumor cells at the primary site while also addressing micrometastatic disease. Concurrent chemoradiation therapy has become standard treatment for many types of locally advanced tumors, including lung, cervical, esophageal, rectal, and anal malignancies. We present a review of clinical trials examining the role of chemoradiation therapy in high-risk prostate cancer.

Head and neck radiotherapy compliance in an underserved patient population.

OBJECTIVES/HYPOTHESIS: Compliance to intensive multiweek radiation therapy (RT) regimens in head and neck cancer (HNC) patients is challenging, particularly among medically underserved patients with fewer financial and social resources. Treatment prolongation reduces local control and overall survival rates, making adherence to treatment a key factor in optimal outcome. We evaluated factors affecting compliance in medically underserved patients who received RT for HNC in a large municipal hospital setting in New York City. STUDY DESIGN: Retrospective review. METHODS: Treatment records of patients treated between July 2004 and August 2008 were reviewed. Number of and reasons for missed treatments were identified. Several demographic, toxicity, and treatment variables were analyzed for impact on compliance. RESULTS: Eighty consecutive HNC patients who underwent RT with a 5- to 7-week regimen were identified. Thirty-two patients (40%) missed no treatments, 36 (45%) missed one to six treatments, six (8%) missed seven to 14 treatments, two (3%) missed more than 14 treatments, and four (5%) did not complete treatment. Reasons for missed treatments were hospitalization (31% of events) and toxicity (20%). Patients with percutaneous endoscopic gastrostomy tube were more likely to miss treatments (P = .01, chi(2) test). No other variable showed a significant association with missed treatments (chi(2) test). CONCLUSIONS: Intensive RT for HNC can be delivered with very good adherence within a medically underserved population. Eighty-five percent of patients completed treatment with 0 to 6 days of interruption. Efforts to further improve adherence in this population are ongoing.

Technical aspects and perspectives of the vaginal mold applicator for brachytherapy of gynecologic malignancies.

PURPOSE: The importance of the quality of cervical cancer brachytherapy applicators has been reported, suggesting a direct influence of competent technical implant performance on outcome. In our institute, an original brachytherapy technique based on the use of a molded applicator for genital tract brachytherapy has been applied routinely in clinical practice. Here, we report the technical aspects of this customized applicator and perspectives on its use. TECHNICAL ASPECTS: The first step consists of a vaginal impression that accurately shows the topography and extension of the tumor as well as the anatomy of the vagina and cervix. From this impression, an acrylic applicator is made. Then, the intended positions of the vaginal catheters are drawn on the surface of the mold by the radiation oncologist. Two plastic vaginal catheters are introduced and fixed on the internal surface of the molded applicator. A hole for the cervical os is made through which the uterine probe will be positioned. PERSPECTIVES: This method allows for high specificity within the framework of a modern brachytherapy procedure, integrating the tumor topography, anatomy of the patient, and internal movements of target and critical volumes. This technique has been successfully extended to other tumor locations, such as genital tract rhabdomyosarcoma in children and postoperative endocavitary brachytherapy in patients with endometrial cancer. CONCLUSION: Customization of a vaginal brachytherapy applicator allows for the maintenance of morphologic optimization throughout the treatment course, which better takes into account a fourth dimension: internal organ motion during the course of brachytherapy.

Toxicity of head-and-neck radiation therapy in human immunodeficiency virus-positive patients.

PURPOSE: To examine the acute morbidity of high dose head and neck RT and CRT in patients with infected with HIV. METHODS AND MATERIALS: All HIV-positive patients who underwent radiation therapy for head and neck cancer in our department between 2004 and 2008 were reviewed. Treatment related data were examined. All treatments were delivered with megavoltage photon beams or electron beams. Patients were evaluated by an attending radiation oncologist for toxicity and response on a weekly basis during therapy and monthly after treatment in a multidisciplinary clinic. Acute toxicities were recorded using the Radiation Therapy and Oncology Group (RTOG) common toxicity criteria. Response to treatment was based on both physical exam as well as post-treatment imaging as indicated. RESULTS: Thirteen patients who underwent RT with a diagnosis of HIV were identified. Median age was 53 years and median follow-up was 22 months. Twelve had squamous cell carcinoma and one had lymphoproliferative parotiditis. Median radiation dose was 66.4 Gy and median duration of treatment was 51 days. The median number of scheduled radiotherapy days missed was zero (range 0 to 7). One patient (8%) developed Grade 4 confluent moist desquamation. Eight patients (61%) developed Grade 3 toxicity. CONCLUSION: Based on our results, HIV-positive individuals appear to tolerate treatment for head and neck cancer, with toxicity similar to that in HIV-negative individuals.