Search

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., (© 2023. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ng, Gregucci, Pennell, Nagar, Golden, Knisely, Sanfilippo and Formenti.)

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., Competing Interests: Declaration of interests NKA reports stock options from TMRW, Angiocrine Bioscience, and View Point Medical; and is on the research advisory committee for AstraZeneca. AS reports personal fees from AstraZeneca, Blueprint Medicines, Genentech, Medtronic, and Takeda. JLP reports leadership and stock options from TMRW, Angiocrine Bioscience, and View Point Medical. BMS reports personal fees from AstraZeneca, Pfizer, Flame Biosciences, Gala Therapeutics, Bristol Myers Squibb, and Ribon Therapeutics; and is on the board of directors for the Lung Cancer Research Foundation. BEL reports personal fees from AstraZeneca. KVB reports personal fees from Janssen, Eli Lilly, Takeda, Johnson and Johnson, Sanfoi, and Ariad. SCF has received grants from Bristol Myers Squibb, Varian, Merck, Eisai, Eli Lilly, Janssen, and Regeneron; and personal fees from Accuray, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Elekta, EMD Serono/Merck, GlaxoSmithKline, Janssen, MedImmune, Merck US, Regeneron, Varian, and ViewRay. PJC was partially supported by a grant from the Clinical and Translational Science Center at Weill Cornell Medical College (grant number 1-UL1-TR002384-01). All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

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.

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.

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/β). 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.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.

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.

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Xeroderma pigmentosum, an autosomal recessive disease that occurs with a frequency of 1:250,000, is caused by a genetic defect in nucleotide excision repair enzymes. Mutation of these enzymes leads to the development of multiple basal cell and squamous cell carcinomas., Objectives: We present a case of xeroderma pigmentosum in a patient with cervical and intraparotid metastatic disease from recurrent cutaneous squamous cell carcinomas of the face and scalp, treated with neck dissection and re-irradiation. With the illustrative case report, we include a literature review of diagnosis, prognostic factors, and treatment, with emphasis on surgical and radiation treatment of cervical metastatic disease from recurrent skin carcinomas., Case Presentation: A xeroderma pigmentosum patient presented to our clinic with a 2-cm right submental and 1-cm right infra-auricular mass after resection of multiple squamous cell carcinomas of the scalp and face, and external-beam radiation therapy to the right face and neck. Fine-needle aspiration biopsy of the submental mass revealed poorly differentiated squamous cell carcinoma. The patient was brought to the operating room for a right modified radical neck dissection and excision of the right submental and intraparotid mass. Surgical pathology revealed 3 level ia and supraclavicular lymph nodes that were positive for metastatic squamous cell carcinoma. Re-irradiation to the entire right hemi-neck and left submandibular nodal region was performed using opposed oblique portals for the upper neck and a low anterior en face hemi-neck portal. The left parotid region was also included in the re-irradiation volume. Treatment was completed without delayed complications or recurrences to date., Conclusions: To our knowledge, this is the first case report in the literature of a patient with xeroderma pigmentosum who subsequently developed metastatic disease from recurrent cutaneous squamous cell carcinoma. Because of the rarity of xeroderma pigmentosum, this case report is also the first to describe re-irradiation to treat cervical and intraparotid metastatic disease in a xeroderma pigmentosum patient.

Purpose: To retrospectively evaluate the prevalence of pterygoid process sclerosis in patients with untreated nasopharyngeal carcinoma., Materials and Methods: This retrospective HIPAA-compliant study was performed after the institutional review board deemed it to be exempt from review and patient informed consent. Contrast material-enhanced computed tomographic (CT) scans of the neck obtained in 31 patients (22 men, nine women; mean age, 42 years; age range, 27-68 years) with untreated nasopharyngeal carcinoma and in 31 control subjects (17 men, 14 women; mean age, 43 years; age range, 19-62 years) were evaluated independently by two neuroradiologists. The presence of sclerosis of the pterygoid process-defined as increased attenuation in the medullary cavity and/or thickening of the cortical bone-was assessed. Other findings noted included pterygoid process erosion, enhancing tumor adjacent to the pterygoid process, and CT evidence of parapharyngeal extension of the tumor. The data were evaluated by using generalized estimating equations based on a binary logistic regression model., Results: The prevalence of pterygoid process sclerosis averaged for the two readers was 60% (37 of 62 subjects) among the patients with nasopharyngeal carcinoma but only 3% (two of 62 subjects) among the control subjects, indicating a highly significantly increased prevalence (P < .001) of this finding in the patients with nasopharyngeal carcinoma. The overall prevalences of pterygoid process erosion, parapharyngeal extension of tumor, and enhancing tumor adjacent to the pterygoid process were 27% (17 of 62 subjects), 47% (29 of 62 subjects), and 77% (48 of 62 subjects), respectively. Pterygoid process sclerosis was the sole skull base abnormality in 36% (11 of 31) of the patients with nasopharyngeal carcinoma., Conclusion: Sclerosis of the pterygoid process, which was present in about half of the patients with untreated nasopharyngeal carcinoma, may reflect tumor proximity to or tumor invasion of the pterygoid process.

Purpose: To analyze the overall pattern of treatment failure and sites of pelvic disease recurrence relative to the radiation fields used in treating patients with clinically staged T4 rectal cancer with preoperative chemoradiation followed by multivisceral resection., Methods and Materials: Between 1990 and 1998, 45 patients with T4 rectal cancer were treated with preoperative chemoradiation. Clinical staging was according to the system of the American Joint Cancer Committee and was based on endoscopic ultrasonography, chemotherapy (CT), and physical examination. A diagnosis of T4 disease required evidence of invasion of a contiguous structure on CT (n = 31) or endorectal ultrasonography (n = 6), vaginal mucosal involvement on pelvic examination (n = 6), or a combination of these findings (n = 2). Chemoradiation was delivered with 18 MV photons using a 3-field belly-board technique. The median total dose was 45 Gy in all patients (range 45-63). Nine patients received a boost with external beam radiotherapy (EBRT) (n = 5, 1.8-18 Gy), intraoperative RT (n = 3, 10-20 Gy), or interstitial brachytherapy (n = 1, 20 Gy). All patients received concurrent chemotherapy consisting of protracted venous infusion 5-fluorouracil (300 mg/m(2), 5 d/wk). Resection was not performed in 13 (29%) of the 45 patients because of metastases detected before resection or patient refusal. Multivisceral resection and pelvic exenteration was required in 21 (66%) and 11 (34%) of 32 patients, respectively. We compared the location of pelvic disease recurrence with the RT simulation films. The Kaplan-Meier method was used to calculate the 4-year actuarial pelvic and distant recurrent rates and the overall survival rate., Results: The median length of follow-up was 31.0 months for all patients and 40.0 months for patients alive at last follow-up. When only the resected cases were considered, the local recurrence rate was 20%. Distant metastases occurred in 44% of cases; the overall survival rate was 69%. When all patients were considered, the local recurrence rate was similar (24%), but the rate of distant recurrence (51%) was higher and the overall survival rate lower (50%). Pelvic disease was controlled in all 8 patients whose disease responded well to chemoradiation (either a histologically complete response or microscopic residual disease). Three of 4 patients with close or positive margins had pelvic recurrences despite intraoperative RT and brachytherapy. Nine of the 10 pelvic recurrences occurred in the radiation field. Elective external iliac nodal irradiation was not used, and nodal metastases were not seen in that region. In 1 case, marginal recurrence occurred in a common iliac node at the superior edge of the treatment field., Conclusions: Despite aggressive multimodality therapy including multivisceral resection, a high rate of pelvic and distant disease recurrence occurred in patients with clinically staged T4 disease. Regional disease recurred almost exclusively in the radiation field. The intraoperative RT and interstitial brachytherapy doses used did not prevent pelvic disease recurrence in patients with close or positive margins. Novel strategies such as higher preoperative doses of RT with or without altered fractionation or more effective radiosensitizers are needed to improve locoregional control in patients with T4 disease. Future strategies must also include more effective systemic therapy.

Introduction/purpose: Surgery and postoperative radiotherapy (XRT) is a standard therapy for locally advanced resectable oropharyngeal carcinoma. This maximizes local-regional control, but does not address the potential for occult distant metastases. Additionally, some patients may suffer poor functional outcome after this intensive local therapy. This report reviews our institutional experience with modern radical surgery and XRT for this disease., Methods: A retrospective chart review was performed on 51 consecutive patients treated from 1991 to 1997 at the University of Pennsylvania with radical surgery and postoperative XRT. This study included patients with locally advanced, stage III/IV (exclusive of T1-2N1) squamous carcinoma of the oropharynx. All patients had a good performance status (ECOG 0-1). Patients who received adjuvant chemotherapy were excluded. No patient had gross residual disease after surgery; the median XRT dose was 63.7 Gy. Survival, local-regional control (LRC), and freedom from distant metastases (DM) were calculated actuarially. In patients who remained free of disease, functional status was determined using the List Performance Status Scale (PSS)., Results: With a median follow-up in surviving patients of 34 months, the 3-year actuarial overall survival was 51%. The 3-year LRC was 73%, and the freedom from DM was 69%. The most significant factor predicting for failure was the number of pathologically positive nodes (P <.001 for survival and DM; P =.003 for LRC). In 29 patients who were evaluable for the List PSS, the mean normalcy-of-diet score was 48; the mean eating-in-public score was 53; and the mean understandability-of-speech score was 75. There was a trend toward better PSS scores in patients with T1-2 tumors versus T3-4 tumors, although this did not reach statistical significance., Conclusions: Surgery and postoperative XRT offer relatively good LRC and moderate overall survival rates. Results, however, remain suboptimal, particularly with respect to the risk of DM and the functional outcome. These data provide a baseline for comparison with maturing results from multimodality trials in which radical surgery is not used in all patients with locally advanced oropharyngeal carcinoma.

Background and Objective: To describe the toxicity of photodynamic therapy (PDT) in patients with carcinoma of the upper aerodigestive tract who received prior treatment with external beam irradiation and intraluminal brachytherapy (IB)., Study Design/materials and Methods: Hospital records of PDT patients were reviewed. Three patients who received prior treatment with external beam irradiation and IB were identified. Two patients had esophageal carcinoma treated with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy) followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications: 630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at 1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one light application: 630 nm, 150 J/cm, 200 mW/cm)., Results: One patient with esophagus cancer had formation of a tracheoesophageal fistula, which required stent placement. The other esophageal cancer patient developed quadriplegia due to an epidural abscess arising from a fistula with the diseased portion of the esophagus. The lung cancer patient had massive hemoptysis after the procedure and died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary artery., Conclusion: Patients with upper aerodigestive tract carcinoma who have received treatment with both external beam irradiation and IB seem to be at higher risk for complications when treated with PDT., (Copyright 2001 Wiley-Liss, Inc.)

Purpose: To assess the clinical outcome and prostate-specific antigen (PSA) response and to determine prognostic factors for biochemical disease-free survival in patients treated with external beam radiotherapy following radical prostatectomy without hormonal therapy., Methods and Materials: Forty-eight patients were treated after prostatectomy with radiotherapy between March, 1988 and December, 1993. Seven patients had undetectable PSA (<0.2) and the remainder had detectable PSA at the time of irradiation (overall: median 2.7, range 0-24.9). Nine patients had biopsy proven local recurrence, palpable local disease, or positive preirradiation imaging. No patients received hormonal therapy prior to irradiation. Median follow-up was 55 months. A median dose of 60 Gy (range 58-66) was given to the prostate bed. Survival was analyzed using the life-table method. Actuarial biochemical disease-free survival was the primary endpoint studied., Results: In patients with detectable PSA, 51% had levels return to undetectable after irradiation. The actuarial 5-year freedom from biochemical failure for all patients was 24%. A significant difference in biochemical disease-free survival was seen for patients irradiated with preirradiation PSA that was undetectable (p < 0.001), or preirradiation PSA that was < or =2.7 (p = 0.002), vs. preirradiation PSA that was >2.7. Five-year actuarial biochemical disease-free survival values were 71, 48, and 0%, respectively, for the three groups. Biochemical disease-free survival was not affected by preoperative PSA level, clinical stage, Gleason's score, pathologic stage, surgical margins, presence of undetectable PSA after surgery, surgery to radiation interval, total dose, or presence of clinically suspicious local disease. Based on digital rectal exam, there were no local failures., Conclusion: Biochemical disease-free survival after postprostatectomy radiation is predicted by the PSA at the time of irradiation. Clinical local control is excellent, but distant failure remains a significant problem in this population. The addition of concomitant systemic therapy should be investigated in patients with PSA >2.7.

Desmoplastic fibroma is a rare, locally aggressive, benign tumor that is considered the skeletal counterpart of the desmoid tumor of soft tissues. Although the treatment of choice of desmoplastic fibroma is surgical excision, radiation therapy should be considered when surgery is not a viable option.