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Objective: To characterize patterns of failure using prostate-specific membrane antigen positron emission tomography (PSMA PET) after radical prostatectomy (RP) and salvage radiotherapy (SRT)., Methods: Patients with rising PSA post-RP+SRT underwent 68 Ga-HBED-iPSMA PET/CT on a single-arm, prospective imaging trial (NCT03204123). Scans were centrally reviewed with pattern-of-failure analysis by involved site. Positive scans were classified using 3 failure categories: pelvic nodal, extra-pelvic nodal or distant non-nodal. Associations with failure categories were analyzed using cumulative incidence and generalized logits regression., Results: We included 133 men who received SRT a median of 20 months post-RP; 56% received SRT to the prostatic fossa alone, while 44% received pelvic SRT. PSMA PET/CT was performed a median of 48 months post-SRT. Overall, 31% of PSMA PET/CT scans were negative, 2% equivocal and 67% had at least 1 positive site. Scan detection was significantly associated with PSA level prior to PSMA PET/CT. Analysis of 89 positive scans demonstrated pelvic nodal (53%) was the most common relapse and fossa relapse was low (9%). Overall, positive scans were pelvic (n = 35, 26%), extra-pelvic nodal (n = 26, 20%) or distant non-nodal failure (n = 28, 21%), and 70% of positive scans were oligorecurrent. We observed similar cumulative incidence for all failure categories and relatively few clinicodemographic associations. Men treated with pelvic SRT had reduced odds of pelvic failure versus exclusive fossa treatment., Conclusion: Pelvic, extra-pelvic nodal, and distant non-nodal failures occur with similar incidence post-SRT. Regional nodal relapse is relatively common, especially with fossa-only SRT. A high oligorecurrence rate suggests a potentially important role for PSMA-guided focal therapies., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer., Methods and Materials: This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months., Results: The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure., Conclusion: Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial reported overall survival benefits for prostate-directed radiation therapy (PDRT) in low-burden metastatic prostate cancer. Oligometastasis-directed radiation therapy (ORT) improves androgen deprivation therapy (ADT)-free and progression-free survivals. Comprehensive PDRT + ORT to all detectable metastases may offer benefit for de novo oligometastatic prostate cancer (DNOPC) and is under prospective study; given few available benchmarks, we reviewed our institutional experience., Methods and Materials: Forty-seven patients with DNOPC with predominantly M1b disease received neoadjuvant, concurrent, and adjuvant ADT plus PDRT + ORT to 1 to 6 oligometastases. Gross pelvic (N1) nodes were not considered oligometastases unless focally targeted without broader nodal coverage. Outcomes were analyzed from radiation therapy (RT) start using Kaplan-Meier, competing risks, and Cox regression. Median follow-up was 27 (95% confidence interval, 16-42) months., Results: At 1- and 2-years post-RT, cumulative incidence of distant metastatic progression (DMP) was 21% and 32%, whereas overall survival was 90% and 87%, respectively. Neuroendocrine/intraductal histology, prostate-specific antigen (PSA) < 20, and detectable PSA after PDRT + ORT were associated with increased DMP risk; number and location of oligometastases were not. Local failure was rare, with 3 prostate recurrences and progression of 10 treated oligometastases during follow-up. After neoadjuvant ADT, 9 (19%) patients had undetectable PSA (<0.05 ng/mL), which increased to 32 (68%) after PDRT + ORT. Overall 2-year incidence of biochemical recurrence (BCR) and development of castrate resistance were 23% and 36%, respectively. Undetectable PSA post-RT was associated with lower risk of BCR (hazard ratio, 0.19; P = .004) and DMP (hazard ratio, 0.26; P = .025). Overall, 23 (49%) patients were trialed off ADT; 16 (70%) had testosterone recovery (>150 ng/dL) and, of these, 5 had subsequent PSA rise and restarted ADT 2 to 21 months postrecovery. The remaining 11 were maintained off ADT without BCR. Median noncastrate duration was 8 months; 7 patients had normalized testosterone for >1 year., Conclusions: A comprehensive, radiotherapeutic-based treatment strategy has favorable clinical outcomes and can produce prolonged noncastrate remissions in a subset with DNOPC., (© 2020 The Authors.)

Purpose: To evaluate physician-reported assessments of an established faculty orientation program for new radiation oncology physicians at a large academic center and to prospectively analyze the effects of an onboarding improvement program based on those assessments., Materials and Methods: An anonymous survey was designed and distributed to physicians new to the department who received onboarding orientation between 2013 and 2017. Survey questions addressed the comprehensiveness, effectiveness, and utility of various orientation activities. On the basis of the survey results, an improved onboarding program was designed and implemented for nine new faculty members between May 2018 and November 2018. A post-intervention survey querying topics similar to those in the pre-intervention survey was distributed to the new faculty members. Descriptive statistics were generated to compare the pre-intervention and post-intervention groups., Results: The overall rate of survey completion was 85% (17 of 20). The intervention program markedly improved physician assessment of comprehensiveness and effectiveness of the onboarding process. Physicians strongly and consistently identified mentor shadowing, on-the-job training, and other faculty mentorship activities as the most important components of an effective onboarding experience., Conclusion: An enhanced, tailored, person-oriented, formal onboarding improvement program significantly increased physician assessment scores of comprehensiveness and effectiveness of the faculty onboarding process. This model can serve as a framework for increasing physician preparedness, encouraging early physician mentorship, and ensuring a universal standard of quality across large practices.

Purpose: The use of magnetic resonance imaging (MRI) for radiation therapy simulation is growing because of its ability to provide excellent delineation of target tissue and organs at risk. With the use of hypofractionated schemes in prostate cancer, urethral sparing is essential; however, visualization of the prostatic urethra can be challenging because of the presence of benign prostatic hyperplasia as well as respiratory motion artifacts. The goal of this study was to compare the utility of 2 motion-insensitive, T2-weighted MRI pulse sequences for urethra visualization in the setting of MRI-based simulation., Methods and Materials: Twenty-two patients undergoing MRI simulation without Foley catheters were imaged on a 3 Tesla MRI scanner between October 2018 and January 2019. Sagittal multislice data were acquired using (1) MultiVane XD radial sampling with parallel imaging acceleration (MVXD) and (2) single-shot fast-spin-echo (SSFSE) sequences with acquisition times of 2 to 3 minutes per sequence. For each examination, 2 genitourinary radiologists scored prostatic urethra visibility on a 1-to-5 scale and rated the signal-to-noise ratio and the presence of artifacts in each series., Results: Urethral visibility was scored higher in the MVXD series than in the SSFSE series in 18 of 22 cases (Reader 1) and 17 of 22 cases (Reader 2). The differences in scores between MVXD and SSFSE were statistically significant for both readers (P < .0001 for both, paired Student's t-test) and interobserver agreement was high (Cohen's kappa = 0.67). Both readers found the signal-to-noise ratio of the MVXD sequence to be superior in all cases. The MVXD sequence was found to generate more artifacts than the SSFSE sequence, but these tended to appear in the periphery and did not affect the ability to visualize the urethra., Conclusions: A radial T2-weighted multislice pulse sequence was superior to an SSFSE sequence for visualization of the urethra in the setting of magnetic resonance simulation for prostate cancer., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer., Methods and Materials: A total of 136 patients were enrolled in a phase 1 dose-escalation study to determine the tolerance of escalating radiation dose levels of SBRT for the treatment of localized prostate cancer. The initial dose level was 32.5 Gy in 5 fractions, and doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy. Eligibility criteria included only patients with low and intermediate risk, and the maximum prostate volume was 60 cm 3 . Patients treated with neoadjuvant androgen deprivation were excluded. The median follow-up in survivors for the 4 dose levels was 5.9, 5.4, 4.1, and 3.5 years, respectively., Results: The incidence of acute grade 2 rectal toxicities for dose levels 1 to 4 were 0%, 2.9%, 2.8%, and 11.4% respectively. No grade 3 or 4 acute rectal toxicities were observed. The incidence of acute grade 2 urinary toxicities for dose levels 1 to 4 were 16.7%, 22.9%, 8.3%, and 17.1%, respectively. No grade 3 or 4 acute urinary toxicities were observed. No grade 2 or higher rectal toxicities were observed. The incidence of late grade 2 urinary toxicities for dose levels 1 to 4 was 23.3%, 25.7%, 27.8%, and 31.4%, respectively. Only 1 late grade 3 urinary toxicity (urethral stricture) developed in the 40-Gy dose arm; the stricture was corrected with transurethral resection. No grade 4 late urinary toxicity was observed. The 5-year cumulative incidence of prostate-specific antigen failure for dose levels 1 to 4 was 15%, 6%, 0%, and 0%. The incidence of a 2-year positive posttreatment biopsy was 47.6%, 19.2%, 16.7%, and 7.7%, respectively for the 4 dose arms (P = .013)., Conclusions: SBRT doses ranging from 32.5 to 40 Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of tumor clearance observed with higher doses., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Multibeam intensity modulated radiation therapy (IMRT) enhances the therapeutic index by increasing the dosimetric coverage of the targeted tumor tissues while minimizing volumes of adjacent organs receiving high doses of RT. The tradeoff is that a greater volume of lung is exposed to low doses of RT, raising concern about the risk of radiation pneumonitis (RP)., Methods and Materials: Between July 2010 and January 2013, patients with node-positive breast cancer received inverse-planned, multibeam IMRT to the breast or chest wall and regional nodes, including the internal mammary nodes (IMNs). The primary endpoint was feasibility, predefined by dosimetric treatment planning criteria. Secondary endpoints included the incidence of RP grade 3 or greater and changes in pulmonary function measured with the Common Terminology Criteria for Adverse Events version 3.0 scales, pulmonary function tests and community-acquired pneumonia questionnaires, obtained at baseline and 6 months after IMRT. Clinical follow-up was every 6 months for up to 5 years., Results: Median follow-up was 53.4 months (range, 0-82 months). Of 113 patients enrolled, 104 completed follow-up procedures. Coverage of the breast or chest wall and IMN was comprehensive (median 48.1 Gy and 48.9 Gy, respectively). The median volume of lung receiving a high dose (V20Gy) and a low dose (V5) was 29% and 100%, respectively. The overall rate of respiratory toxicities was 10.6% (11/104), including 1 grade 3 RP event (0.96%). No differences were found in pulmonary function test or community-acquired pneumonia scores after IMRT. The 5-year rates of locoregional recurrence-free, disease-free, and overall survival were 93.2%, 63.6%, and 80.3%, respectively., Conclusions: Multibeam IMRT in patients with breast cancer receiving regional nodal irradiation was dosimetrically feasible, based on early treatment planning criteria. Despite the large volume of lung receiving low-dose RT, the incidence of grade 3 RP was remarkably low, justifying inverse-planned IMRT as a treatment modality for patients with high-risk breast cancer in whom conventional RT techniques prove inadequate., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to examine patterns of failure and the relationship to radiation doses in patients with head and neck carcinoma of unknown primary (HNCUP)., Methods: We reviewed 85 patients with HNCUP treated with curative-intent radiation therapy (RT) during 1995 to 2012., Results: There have been no failures in the pharyngeal axis. Relapse at initial neck sites of disease developed in 7 patients (8.2%). The median dose to these sites was 70 Gy (range, 63-70 Gy). Failure at neck sites without initial disease occurred in 4 patients (4.7%). The median dose was 54 Gy (range, 50-58.8 Gy). There were no contralateral failures in a small cohort of patients receiving unilateral treatment (n = 6). Percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months was 7.4%, and 2.5% at 3 years. Esophageal stricture developed in 5 patients (5.9%)., Conclusion: RT for HNCUP produces excellent locoregional control rates with acceptably low levels of late toxicity. Doses prescribed to sites of eventual failure did not vary significantly from those sites that were treated and remain in control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E426-E431, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Although intensity-modulated radiotherapy (IMRT) is a standard of care for many head and neck cancers, its use for carotid-sparing (CS) therapy in early-stage laryngeal carcinoma is controversial., Methods: 330 consecutive patients with early-stage laryngeal carcinoma were treated from 1/1989 to 5/2011, including 282 conventional radiotherapy (CRT) and 48 CS-IMRT patients. The median follow-up was 43 (CS-IMRT) and 66 (CRT) months., Results: There was no difference in local failure rates comparing patients undergoing CS-IMRT with CRT, with 3-year local control rates of 88% vs. 89%, respectively (p=0.938). Using a 1cm circumferential margin, the average dose to the left and right carotid arteries was 48.3 and 47.9 Gy, respectively. 88% of locoregional recurrences involved the ipsilateral true vocal cord, including all local recurrences in the IMRT group., Conclusions: These results warrant further prospective evaluation of CS-IMRT for early-stage glottic larynx cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: A retrospective analysis of the outcomes of stereotactic body radiation therapy (SBRT) in the treatment of large (>3 cm) non-small-cell lung cancers (NSCLCs)., Methods: Between February 2007 and November 2011, 63 patients with T2-T4N0 NSCLC were treated with SBRT. Toxicity was graded per Common Terminology Criteria for Adverse Events, version 4.0. Local failure-free survival (LFFS), recurrence-free survival, and overall survival curves were estimated using the Kaplan-Meier method and univariate analysis was performed using Cox regression., Results: Median follow-up was 16.9 months. One- and 2-year LFFS was 88.8% and 75.7%, 1- and 2-year recurrence-free survival was 59.0% and 41.6%, and 1- and 2-year overall survival was 77.1% and 57.6%, respectively. Planning target volume less than 106 cm was associated with a significantly higher 1- and 2-year LFFS (p =0.05). Grade 2 or higher acute and late pulmonary toxicities occurred in 19.3% and 19.3% of patients, respectively, and were not associated with common dose-volume parameters; 22.8% of patients developed grade 2 or higher chest wall pain, which was significantly associated with chest wall V30 70 cm or more (p = 0.03)., Conclusions: SBRT for larger NSCLC tumors achieves high LFFS with acceptable toxicity. LFFS was worse with planning target volume 106 cm or more. Grade 2 or higher chest wall pain was associated with chest wall V30 70 cm or more.

Nearly 25% of patients diagnosed with early-stage non-small cell lung carcinomas (NSCLC) are medically inoperable. For these patients, the radial stereotactic body radiation therapy (SBRT), planned and delivered with intensity modulated radiation therapy (IMRT) techniques, offers the only curative option. However, IMRT-SBRT has three significant deficiencies: an elevated beam-on time (MU); a reduced MU-to-cGy coefficient; and a prolonged delivery time. To address these issues, we have developed our in-house version of volumetric modulated arc therapy (VMAT). In this preliminary study, we compared VMAT-SBRT with IMRT-SBRT in terms of optimization, dosimetry, and delivery. Our goal was to investigate the feasibility of replacing the exiting IMRT-SBRT with VMAT-SBRT as a safe and viable alternative radiation modality for early-stage NSCLC.

Recent theoretical studies and clinical investigations have indicated that volumetric modulated arc therapy (VMAT) can produce equal or better treatment plans than intensity modulated radiation therapy (IMRT), while achieving a significant reduction in treatment time. Built upon the concept of aperture-based multi-level beam source sampling optimization, VMAT has overcome many engineering constraints and become a clinically viable radiation treatment modality. At this point in time, however, there are only two commercial VMAT treatment planning systems (TPS) on the market, which severely limit the dissemination of this novel technology. To address this issue, we recently have successfully developed our own version of VMAT TPS. In this paper, we present our preliminary test results.

This paper reviews recent advances in 4D medical imaging (4DMI) and 4D radiation therapy (4DRT), which study, characterize, and minimize patient motion during the processes of imaging and radiotherapy. Patient motion is inevitably present in these processes, producing artifacts and uncertainties in target (lesion) identification, delineation, and localization. 4DMI includes time-resolved volumetric CT, MRI, PET, PET/CT, SPECT, and US imaging. To enhance the performance of these volumetric imaging techniques, parallel multi-detector array has been employed for acquiring image projections and the volumetric image reconstruction has been advanced from the 2D to the 3D tomography paradigm. The time information required for motion characterization in 4D imaging can be obtained either prospectively or retrospectively using respiratory gating or motion tracking techniques. The former acquires snapshot projections for reconstructing a motion-free image. The latter acquires image projections continuously with an associated timestamp indicating respiratory phases using external surrogates and sorts these projections into bins that represent different respiratory phases prior to reconstructing the cyclical series of 3D images. These methodologies generally work for all imaging modalities with variations in detailed implementation. In 4D CT imaging, both multi-slice CT (MSCT) and cone-beam CT (CBCT) are applicable in 4D imaging. In 4D MR imaging, parallel imaging with multi-coil-detectors has made 4D volumetric MRI possible. In 4D PET and SPECT, rigid and non-rigid motions can be corrected with aid of rigid and deformable registration, respectively, without suffering from low statistics due to signal binning. In 4D PET/CT and SPECT/CT, a single set of 4D images can be utilized for motion-free image creation, intrinsic registration, and attenuation correction. In 4D US, volumetric ultrasonography can be employed to monitor fetal heart beating with relatively high temporal resolution. 4DRT aims to track and compensate for target motion during radiation treatment, minimizing normal tissue injury, especially critical structures adjacent to the target, and/or maximizing radiation dose to the target. 4DRT requires 4DMI, 4D radiation treatment planning (4D RTP), and 4D radiation treatment delivery (4D RTD). Many concepts in 4DRT are borrowed, adapted and extended from existing image-guided radiation therapy (IGRT) and adaptive radiation therapy (ART). The advantage of 4DRT is its promise of sparing additional normal tissue by synchronizing the radiation beam with the moving target in real-time. 4DRT can be implemented differently depending upon how the time information is incorporated and utilized. In an ideal situation, the motion adaptive approach guided by 4D imaging should be applied to both RTP and RTD. However, until new automatic planning and motion feedback tools are developed for 4DRT, clinical implementation of ideal 4DRT will meet with limited success. However, simplified forms of 4DRT have been implemented with minor modifications of existing planning and delivery systems. The most common approach is the use of gating techniques in both imaging and treatment, so that the planned and treated target localizations are identical. In 4D planning, the use of a single planning CT image, which is representative of the statistical respiratory mean, seems preferable. In 4D delivery, on-site CBCT imaging or 3D US localization imaging for patient setup and internal fiducial markers for target motion tracking can significantly reduce the uncertainty in treatment delivery, providing improved normal tissue sparing. Most of the work on 4DRT can be regarded as a proof-of-principle and 4DRT is still in its early stage of development.

Intensity modulated radiation therapy (IMRT) has been widely used in the treatment of lung cancer. The highly conformal dose distribution with steep gradients could miss the target if respiratory motion is not carefully considered during the treatment planning. The issue becomes particularly critical when dose escalation technique is used. To account for this periodical respiratory motion, the common practice is to add an empirical population-based safety margin to the clinical target volume (CTV). However, such a uniform margin does not reflect the fact that respiratory motion is not isotropic. In addition, it is not tailored to each individual patient. Thus, it is not optimal in both tumor targeting and normal tissue sparing. Here, we present our approach to 4D radiation therapy using the Bellows tracking system for targeting mobile lung tumors. The objective was to develop a clinically viable procedure for routine 4D treatment planning.

In order to protect urethra in radiation therapy of prostate cancer, the urethra must be identified and localized as an organ at risk (OAR) for the inverse treatment planning in intensity modulated radiation therapy (IMRT). Because the prostatic urethra and its surrounding prostate tissue have similar physical characteristics, such as linear attenuation coefficient and density, it is difficult to distinct the OAR from the target in CT images. To localize the urethra without using contrast agent or additional imaging modalities other than planning CT images, a different approach was developed using a standard atlas of human anatomy image. This paper reports an investigation, in which an adult urethra was modeled based on a human anatomic image. An elastic model was build to account for a uniform tissue deformation of the prostate. This model was then applied to patients to localize their urethras and preliminary results are presented.

Purpose: To evaluate pleurectomy/decortication (P/D) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM)., Methods and Materials: In a retrospective review, we included MPM patients treated with P/D and adjuvant RT at Memorial Sloan-Kettering Cancer Center from 1974 to 2003. When indicated, patients received intraoperative brachytherapy to residual tumor., Results: All 123 patients received external beam RT (median dose, 42.5 Gy; range, 7.2-67.8 Gy) to the ipsilateral hemithorax postoperatively. Fifty-four patients underwent brachytherapy (matched peripheral dose, 160 Gy). The median and 2-year overall survival for all patients was 13.5 months (range, 1-199 months) and 23%, respectively. One-year actuarial local control for all patients was 42%. Multivariate analysis for overall survival revealed radiation dose <40 Gy (p = 0.001), nonepithelioid histology (p = 0.002), left-sided disease (p = 0.01), and the use of an implant (p = 0.02) to be unfavorable. Two patients (1.6%) died from Grade 5 toxicity within 1 month of treatment., Conclusions: Pleurectomy/decortication with adjuvant radiotherapy is not an effective treatment option for patients with MPM. Our results imply that residual disease cannot be eradicated with external RT with or without brachytherapy and that a more extensive surgery followed by external RT might be required to improve local control and overall survival.

Purpose: The treatment of malignant pleural mesothelioma remains a therapeutic challenge, with median survival rates of about 12 months and local failure rates of up to 80%. Our institution recently published results showing that extrapleural pneumonectomy (EPP) followed by hemithoracic radiation yielded excellent local control. This paper reports our technique for high-dose hemithoracic radiation after EPP., Methods: Between 1990 and 2001, 35 patients with malignant pleural mesothelioma were treated with EPP followed by hemithoracic radiation therapy (median dose: 54 Gy, range: 45-54 Gy) at Memorial Sloan-Kettering Cancer Center. EPP was defined as en bloc resection of the entire pleura, lung, and diaphragm with or without resection of the pericardium. The radiation therapy target volume was the entire hemithorax, including the pleural folds and the thoracotomy and chest tube incision sites. Patients were treated with a total dose of 5400 cGy delivered in 30 fractions of 180 cGy. Radiation therapy was well tolerated, and toxicity data are described., Results: Of the 35 patients analyzed, 29 patients were male, and 18 had right-sided tumors. Twenty-six had epithelioid histologies. UICC stage was I in 4, II in 11, III in 19, and IV in 1 patient. As shown by axial and sagittal isodose distributions, we were able to deliver adequate doses to the target volume while limiting dose to critical structures such as heart, spinal cord, liver, and stomach. The most common toxicities were RTOG Grades 1 and 2 nausea and vomiting, as well as lung, esophageal, and skin toxicities., Conclusion: Extrapleural pneumonectomy followed by high-dose hemithoracic radiation therapy is a feasible treatment regimen that is well tolerated for patients with malignant mesothelioma. We have demonstrated adequate dose distributions, using a combined photon and electron technique with blocking of critical normal structures.

Objective: To determine the outcome for patients with recurrent gynecologic tumors treated with radical resection and combined high-dose intraoperative radiation therapy (HDR-IORT)., Methods and Materials: Between November 1993 and June 1998, 17 patients with recurrent gynecologic malignancies underwent radical surgical resection and high-dose-rate brachytherapy. The mean age of the study group was 49 years (range 28-72 years). The site of the primary tumor was the cervix in 9 (53%) patients, the uterus in 7 (41%) patients, and the vagina in 1 (6%) patient. The treatment for the primary disease was surgery with or without adjuvant radiation in 14 (82%) patients and definitive radiation in 3 (18%) patients. The current surgery consisted of exenterative surgery in 10 (59%) patients and tumor resection in 7 (41%) patients. Complete gross resection was achieved in 13 (76%) patients. The mean HDR-IORT dose was 14 Gy (range 12-15). Additional radiation in the form of permanent Iodine-125 implant was given to 3 of 4 patients with gross residual disease. The median peripheral dose was 140 Gy., Results: With a median follow-up of 20 months (range 3-65 months), the 3-year actuarial local control (LC) rate was 67%. In patients with complete gross resection, the 3-year LC rate was 83%, compared to 25% in patients with gross residual disease, p < 0.01. The 3-year distant metastasis disease-free and overall survival rates were 54% and 54%, respectively. The complications were as follows: gastrointestinal obstruction, 4 (24%); wound complications, 4 (24%); abscesses, 3 (18%); peripheral neuropathy, 3 (18%); rectovaginal fistula, 2 (12%); and ureteral obstruction, 2 (12%)., Conclusion: Radical surgical resection and combined IORT for patients with recurrent gynecologic tumors seems to provide a reasonable local-control rate in patients who have failed prior surgery and/or definitive radiation. Patient selection is very important, however, as only those patients with complete gross resection at completion of surgery appear to benefit most from this radical approach in the salvage setting.

Purpose: Dose escalation using three-dimensional conformal radiation therapy (3D-CRT) has been investigated as a means to improve local control. However, with higher doses, the risk of toxicity increases. Early in our experience, we ceased treating elective nodal areas (lymph node stations without evidence of tumor involvement) in an effort to decrease toxicity while treating the gross tumor to higher doses. This report measures the rate of regional failure without elective radiation therapy to uninvolved lymph nodes., Methods and Materials: A total of 171 patients with non-small-cell lung cancer treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center between 1991 and 1998 were reviewed. Only lymph node regions initially involved with tumor either by biopsy (55%) or radiographic criteria (node > or =15 mm in the short axis on CT) were included in the clinical target volume. Elective nodal failure was defined as a recurrence in an initially uninvolved lymph node in the absence of local failure., Results: Only 11 patients (6.4%) with elective nodal failure were identified. With a median follow-up of 21 months in survivors, the 2-year actuarial rates of elective nodal control and primary tumor control were 91% and 38%, respectively. In patients who were locally controlled, the 2-year rate of elective nodal control was 85%. The median time to elective nodal failure was 4 months (range, 1-19 months). Most patients failed in multiple lymph node regions simultaneously., Conclusion: Local control remains one of the biggest challenges in the treatment of non-small-cell lung cancer. Most patients in our series developed local failure within 2 years of radiation therapy. The omission of elective nodal treatment did not cause a significant amount of failure in lymph node regions not included in the clinical target volume. Therefore, we will continue our policy of treating mediastinal lymph node regions only if they are clinically involved with tumor.

Purpose: Conventional radiotherapeutic techniques are associated with lung toxicity that limits the treatment dose. Motion of the tumor during treatment requires the use of large safety margins that affect the feasibility of treatment. To address the control of tumor motion and decrease the volume of normal lung irradiated, we investigated the use of three-dimensional conformal radiation therapy (3D-CRT) in conjunction with the deep inspiration breath-hold (DIBH) technique., Methods and Materials: In the DIBH technique, the patient is initially maintained at quiet tidal breathing, followed by a deep inspiration, a deep expiration, a second deep inspiration, and breath-hold. At this point the patient is at approximately 100% vital capacity, and simulation, verification, and treatment take place during this phase of breath-holding., Results: Seven patients have received a total of 164 treatment sessions and have tolerated the technique well. The estimated normal tissue complication probabilities decreased in all patients at their prescribed dose when compared to free breathing. The dose to which patients could be treated with DIBH increased on average from 69.4 Gy to 87.9 Gy, without increasing the risk of toxicity., Conclusions: The DIBH technique provides an advantage to conventional free-breathing treatment by decreasing lung density, reducing normal safety margins, and enabling more accurate treatment. These improvements contribute to the effective exclusion of normal lung tissue from the high-dose region and permit the use of higher treatment doses without increased risks of toxicity.

Purpose and Objective: Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer., Patients and Methods: Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme., Results: Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months., Discussion: Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

Objective: The aims of this study were to assess the early and late toxicities of multiple-daily-fraction whole pelvic radiation plus concurrent chemotherapy with either hydroxyurea or 5-fluorouracil (5-FU)/cisplatin and to determine the maximum tolerated external radiation dose in conjunction with brachytherapy, when given with either of these drug regimens, as treatment for locally advanced carcinoma of the cervix., Methods: The first study (GOG 8801) of 38 patients utilized hydroxyurea as a single oral dose of 80 mg/kg to a maximum of 6 g at least 2 h prior to a radiation treatment twice every week. In the second study (GOG 8901) of 30 patients, cisplatin and 5-FU were used concomitantly with radiotherapy. Fifty milligrams per square meter of cisplatin was administered on days 1 and 17 of external radiation. 5-FU was given by continuous intravenous infusion at a dose of 1000 mg/m(2)/day for 4 consecutive days on days 2, 3, 4, 5, and 18, 19, 20, and 21 of external radiation therapy. Both studies utilized external radiation given by an accelerated hyperfractionated regimen of 1.2 Gy per fraction, two fractions per day. All patients were treated 5 days per week with a minimum of 4 h between fractions., Results: Acute toxicity was manageable on both protocols but nausea, vomiting, and myelosuppression were more severe with hydroxyurea. Chronic toxicity was primarily enteric and appeared to be dose-related. There was no obvious correlation seen between pelvic failure rates and the radiation dose or between the chemotherapy regimens used., Conclusions: The defined maximal tolerated dose of whole pelvic radiation was 57.6 Gy in 48 fractions which could be delivered in a hyperfractionated setting with concomitant chemotherapy, followed by brachytherapy. Follow-up is now sufficient that further adverse events should be rare., (Copyright 1999 Academic Press.)

Purpose/objective: This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation., Methods and Materials: Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans., Results: The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (+/- 0.9) mm and inter breath-hold reproducibility of 2.5 (+/- 1.6) mm, as determined from diaphragm position. Patients were able to perform 10-13 breath-holds in one session, with a comfortable breath-hold duration of 12-16 s., Conclusion: Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Purpose: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT)., Methods and Materials: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo)., Results: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery., Conclusion: HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.

In vitro studies and clinical experience have suggested that patients with platinum-refractory epithelial ovarian carcinoma exhibit cross-resistance to radiation. Salvage with radiation in these patients is rare. However, radiation is often utilized to palliate symptoms caused by these chemotherapy-resistant tumors. Forty-seven patients with platinum-refractory epithelial ovarian carcinoma were referred for palliative radiation and 33 (70%) were evaluable for response. One to four regimens of platinum-based chemotherapy (median 2.7) were given to each patient prior to radiation therapy. Of the 33 evaluable patients, 23 (69.7%) had a complete resolution of symptoms after radiation, 8 (24%) had a partial resolution, and 2 were unassessable because of unrelated medical complications. The median duration of response was 11 months (range 1-86) and closely approximated their survival. Thirteen of 33 patients (39%) obtained relief of symptoms for greater than 12 months, with 10 of 33 (30%) having symptoms controlled for 6 to 12 months. In only 10 patients (30%) was the duration of palliation less than or equal to 6 months. Four patients required reirradiation to the same area for recurrence of their symptom. External-beam radiation therapy can provide effective and durable palliation of symptoms in platinum-refractory epithelial ovarian carcinoma patients.

We evaluated the effect of multiple treatment- and disease-related variables on the outcome of patients receiving whole-brain radiation therapy (WBRT) for metastatic gestational trophoblastic disease (GTD). Between November 1967 and December 1994, 21 patients were treated at our institution for GTD metastatic to the brain. All received WBRT, of median 2200 cGy (range 200-3600 cGy). Median follow-up, from date of diagnosis of brain metastases, was 77 months (range 11-170 months). The 5-year actuarial local control of initial brain metastases with > or = 2200 cGy was 91%, compared to 24% with < 2200 cGy (P = 0.05). The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100 and 83%, respectively, compared to 8 and 0%, respectively, for the 12 whose extracranial disease was not controlled (P = 0.0002). Four (33%) of the patients with persistent or progressive extracranial disease later developed new sites of brain metastases, compared to 0% of the patients whose extracranial disease was controlled (P = 0.05). Eleven patients progressed at their initial site(s) of brain metastasis or developed new intracranial lesions; 6 of them died of brain metastases. Survival of patients with GTD metastatic to the brain is excellent if extracranial disease can be controlled. The total dose of radiation is critical in achieving control of initial brain metastases. Patients with uncontrolled extracranial disease are more likely to develop new brain metastases. Salvage of intracranial failures after WBRT is rare.

This article reviews the indications, techniques, and results of brachytherapy in the treatment of non-small cell lung cancer (NSCLC) and selected chest neoplasms. Various isotopes and techniques are used to place radioactive sources directly into a tumor, tumor bed, or the chest. Brachytherapy techniques can be tailored to the clinical situation and can be in the form of permanent interstitial volume or planar implants (radioactive sources permanently imbedded into the tumor or tumor bed) or in the form of temporary interstitial or endoluminal implants (where radioactive sources irradiate a tumor bed over a certain length of time and then are removed). These treatments can be delivered over a short interval (high-dose rate [HDR]) or over a more protracted time (low-dose rate). HDR treatments can be used intraoperatively to deliver a large dose of radiation to a determined target area with selective sparing of surrounding normal structures. Different methods of delivering HDR intraoperative radiation are under investigation. Most reports on brachytherapy for chest malignancies are retrospective and come from a few single institutions. Most of the published data relate to the treatment of NSCLC, but other intrathoracic malignancies, such as malignant pleural mesothelioma and malignant thymoma, have been treated with brachytherapy. To our knowledge, no major randomized trials accurately assess or confirm these retrospective studies yet, complicating the interpretation of these results. Nevertheless, brachytherapy is of value in selected situations and offers the clinician and the patient an innovative method of delivering conformal high-dose radiation to a defined target with preferential sparing of normal surrounding structures. With continued innovations in the development of radioactive isotopes, computerized treatment planning and targeting, and source delivery, brachytherapy should continue to offer an attractive alternative and complement to conventional treatment approaches, and may offer patients improved local control and survival.

Thirty-eight patients with Stage I and II uterine carcinosarcoma were treated by surgery with and without whole-pelvic irradiation (WPI) at our institution from 1975 to 1993. Ten patients (8 Stage I and 2 Stage II) were treated with surgery alone, while 28 patients (20 Stage I and 8 Stage II) received WPI in addition to surgery. With a median follow-up of 75 months (range 25-220 months), a trend toward a decreased rate of pelvic recurrence in those receiving WPI (6/28, 21%) compared to those treated with surgery alone (5/10, 50%) was observed (P = 0.09). There was no difference in the rate of distant recurrence between those receiving WPI (12/28, 43%) and those who did not (4/10, 40%) (P = 0.9). There was also no difference in the 2- and 5-year Kaplan-Meier survival estimates for the patients receiving WPI (79 and 59%, respectively) compared to those who did not receive WPI (60 and 60%, respectively) (P = 0.84). In this small series, the addition of whole-pelvic irradiation to primary surgery did not improve survival; however, a trend toward improved pelvic control was observed, suggesting a possible benefit for pelvic irradiation that should be studied in future trials.

Purpose: The purpose of this study was to assess the feasibility of 103Pd brachytherapy in the management of primary unresectable carcinoma of the pancreas., Methods and Materials: Between August 1988 and January 1992, 11 patients with biopsy-proven primary unresectable adenocarcinoma of the pancreas were treated with 103Pd brachytherapy during laparotomy. The median age was 66 (range 57-70). The most common presenting symptoms were weight loss (eight patients), pain (six patients), and nausea/vomiting (four patients). Less common symptoms were jaundice (two patients), early satiety (two patients), and ascites (one patient). All patients underwent laparotomy and surgical staging. Eight patients had T3N0M0 disease, two patients had T3N1M0 disease, and one patient had T3N1M1 disease. The surgical procedure performed was biliary bypass in six patients, biopsy only in four patients, and gastric bypass in one patient. The average tumor dimension was 4.0 cm. The median activity, matched peripheral dose (MPD) and implanted volumes were 95.3 mCi, 124.4 Gy, and 33 cm3, respectively. The median initial dose rate was 0.21 Gy per hour. Five patients received postoperative external beam radiation therapy (median 45 Gy) and seven patients received chemotherapy postoperatively. The median follow-up was 7 months (range 1-19)., Results: The median survival for the entire group of patients was 6.9 months. Ten of 11 patients have died, with 1 patient presently alive and receiving chemotherapy for metastatic disease to the liver, but without local progression radiographically. Five of 11 patients (45%) were locally controlled, defined as either a complete response or freedom from progression at the site of the implant as evaluated by computed tomography scan. In the other six patients, the median time to local progression was 6.9 months. Five patients developed distant metastases (four liver, one subcutaneous nodule). Two patients failed in regional sites (one omentum, one paraaortic lymph node). Four of 11 patients (36%) developed acute postoperative complications that included one gastric outlet obstruction, one duodenal perforation, and two with sepsis. One of 11 patients (9%) developed a late complication of radiation enteritis 5 months after implantation. The median survival for patients experiencing complications was 1.7 months as compared to 8.4 months for the patients who did not develop a complication (p = 0.10). Pain relief was obtained in five out of six (83%) of the patients presenting with pain for a median duration of 24 weeks. Local control did not appear to be related to the MPD, dose rate, implanted volume, treatment with external beam irradiation, or the use of chemotherapy. Patients were more likely to develop a complication if the MPD was greater than 115 Gy (four out of six patients) as compared to those whose MPD was less than 115 Gy (one out of five patients) (p = 0.12)., Conclusions: Because there was no improvement in median survival over conventional modalities, and the complication rate was high; we do not recommend 103Pd brachytherapy as a component of the treatment of unresectable adenocarcinoma of the pancreas.

Objective: To review the clinicopathologic characteristics of vulvovaginal soft-tissue sarcomas, and to correlate these variables with response to treatment., Methods: We performed a retrospective review of the records of 24 women treated at Memorial Hospital for sarcoma of either the vulva or vagina over 20 years (1974-1993). Archival pathology specimens were reviewed to confirm the diagnosis, histology, and grade of the tumor., Results: Fifteen patients had sarcomas arising from the vagina and nine had primary vulvar tumors. Leiomyosarcoma was the most common histology (n = 13). Twenty-three of 24 women underwent surgical excision as their primary therapy. Twenty-three were available for follow-up, and 16 of them (70%) are free of disease at a median follow-up time of 47 months (range 12-156, mean 59). Five women died of progressive disease and two are currently alive with persistent or recurrent disease. Grade was the most important predictor of outcome; all seven women with low-grade tumors are alive without evidence of disease., Conclusion: Soft-tissue sarcomas are rare tumors of the lower genital tract. The primary therapy is surgical; adjuvant radiation therapy is indicated for high-grade tumors and locally recurrent low-grade sarcomas.

Thirty-five patients with persistent or recurrent epithelial ovarian cancer were treated with salvage pelvic or para-aortic radiotherapy for disease limited to the pelvis (29), para-aortic retroperitoneum (5), or vaginal cuff (1). Prior therapy included a median of 3 chemotherapeutic drugs (range, 1-7) over a median of 12 cycles (range, 5-39); 12 patients had received intraperitoneal chemotherapy. The median number of prior laparotomies was 3 (range, 2-5). Including pelvic boosts, the median dose delivered to the treatment field was 4600 cGy (range 4000-7000); 2 patients received additional treatment with a permanent 125I implant. All patients completed therapy, although 5 (14%) with grade 3 toxicity required a treatment break. Late bowel complications unrelated to recurrence occurred in 3 patients (9%). Median actuarial and progression-free survivals for all patients from start of radiotherapy were 40 and 14 months, respectively. At least 16 of 26 (62%) recurrences involved the treatment field. Multiple prognostic factors were evaluated in terms of recurrence, survival, and acute and chronic complications, but no significant prognosticators were detected. These findings indicate that limited-field salvage radiotherapy has an acceptable complication rate and may prolong the symptom-free survival interval in selected patients.

During the past decade, intraperitoneal therapy of ovarian cancer has evolved from a pharmacologic model into an established treatment technique for women with this malignancy. Approximately 40% of patients with small-volume residual ovarian cancer (microscopic disease or macroscopic tumor, < or = 0.5 cm in maximum tumor diameter), after an objective response to initial organoplatinum-based systemic chemotherapy, may have a surgically documented complete response to platinum-based intraperitoneal chemotherapy. Patients who have not responded to systemic platinum administration rarely will respond to the drug given intraperitoneally, despite the presence of only small-volume residual disease when this regional treatment strategy is used. Other agents with antineoplastic activity after intraperitoneal administration in women with ovarian cancer include mitoxantrone, taxol, alpha-interferon and gamma-interferon, and interleukin-2. Although intraperitoneal therapy currently is being examined as a component of the initial chemotherapeutic program for patients with ovarian cancer, a precise role for regional drug delivery in this clinical setting remains to be defined.

Seventy-seven patients with endometrial cancer with cervical involvement were treated at Memorial Sloan-Kettering Cancer Center from 1968 to 1982. Fractional curettage specimens showed that 25 patients (32%) had involvement of cervical stroma and 52 (68%) had only detached fragments of carcinoma present in endocervical curettings. Six patients treated for palliation only are excluded from analysis of treatment and survival. Our preferred treatment during the time interval studied consisted of preoperative whole pelvic radiotherapy followed by modified radical hysterectomy and bilateral salpingo-oophorectomy with post-operative intravaginal brachytherapy. This regimen was well tolerated by the 37 patients so treated. The remaining patients were treated with a variety of regimens, most commonly radiotherapy and simple hysterectomy (25 patients). With a mean follow-up among survivors of 97 months, disease-free survival is 72%. Mean time to relapse was 19 months, with 90% of relapses occurring within 40 months. Initial sites of relapse included abdomen, 9 (12.6%); lungs, 8 (11.3%); brain, 2 (2.8%); lateral pelvis, 2 (2.8%); and bone, 1 (1.4%). Clinicopathologic variables significantly related to risk of relapse included presence of extrauterine disease at surgery (P = 0.0001), extent of cervical involvement as determined prior to hysterectomy (P = 0.001), depth of myometrial invasion (P = 0.005), and papillary serous histology (P = 0.0002). Treatment of endometrial cancer with cervical involvement with combinations of radiotherapy and surgery is well tolerated and results in an excellent long-term disease-free survival and a low rate of pelvic relapse.

This retrospective analysis of 49 cases of primary carcinoma of the vagina treated with radiation therapy alone from 1970-1988 examines the results of treatment with an emphasis on the importance of brachytherapy technique. Thirty-six patients were treated with combined external beam radiation and brachytherapy, 11 patients were treated with external beam alone, and two patients were treated with brachytherapy alone. Brachytherapy techniques used included intracavitary implants, temporary Ir-192 interstitial implants, and permanent I-125 interstitial implants. Intracavitary therapy included the use of a fractionated high dose rate intravaginal cylinder, tandem and ovoids, and a low dose rate intravaginal cylinder. The 5-year actuarial survival was 44% for Stage I (six patients), 48% for Stage II (27 patients), 40% for Stage III (10 patients), and 0% for Stage IVa and IVb (six patients). There was a significant increase in the 5-year actuarial survival for those patients who had brachytherapy as part of their treatment compared to those patients treated with external beam alone (50% vs. 9%) (p < .001). For Stages II and III, there was a trend toward improved actuarial and crude disease free survival with the use of a temporary Ir-192 interstitial implant as part of the treatment compared to the use of intracavitary brachytherapy as part of the treatment (80% vs. 45%) (p = 0.25) and (75% vs. 44%) (p = 0.08), respectively. Brachytherapy plays an important role in the management of primary vaginal cancer. A temporary interstitial implant should be used over an intracavitary form of therapy for more invasive disease.

Because of their proximity to nerve roots and the spinal cord, it is frequently difficult to achieve complete resection of paraspinal tumors. We have used brachytherapy in an attempt to prevent local recurrence and its associated neurological sequelae. This report analyzes our experience with 35 patients to determine the feasibility, optimal techniques, and efficacy of this approach. The tumor types were non small-cell lung cancer (18), sarcomas (9), and other tumor types (8). Temporary, single plane implants using Ir-192 (median minimum peripheral dose 3000 cGy) were used in 21 patients, and permanent I-125 implants were used in 14 cases (median matched peripheral dose 12,500 cGy). Local control was achieved in 51% (18/35). However, local control was poor when lung cancers were implanted and in cases where the dura was exposed. Radiation myelitis did not occur despite the combined effects of previous external beam radiotherapy (N = 21) and brachytherapy. Our experience demonstrates that combined surgery and paraspinal brachytherapy can be performed with acceptable toxicity and is reasonably effective in preventing local relapse and its neurologic sequelae, particularly for tumors other than lung cancers.