Dramatic Response to Concurrent Anti-PD-1 Therapy and Radiation in Resistant Tumors with Sarcomatoid Differentiation.

A substantial fraction of patients demonstrate resistance to immune checkpoint inhibitors, which limits their use. Use of radiation concurrently with checkpoint inhibitors has been shown to boost immune responsiveness, resulting in significant tumor regression in patients with metastatic melanoma. However, it is unknown whether radiation could play a role in reversing the inherent resistance to checkpoint inhibition in certain tumor types. Most trials testing this concurrent approach exclude such modestly responsive tumors and pursue checkpoint inhibition using anti-cytotoxic T-lymphocyte-associated protein 4 antibody (anti-CTLA-4, ipilimumab). The efficacy of anti-programmed-death-1 (anti-PD-1) therapy when used concurrently with radiation is less known but remains an attractive option due to less autoimmune toxicity compared with CTLA-4 inhibition. In this first reported experience, we have safely and effectively combined anti-PD-1 therapy (nivolumab) concurrently with radiation to treat two patients with relapsed sarcomatoid renal carcinoma and heavily pretreated pleomorphic sarcoma. Both patients experienced a dramatic response that was durable.

Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial.

PURPOSE: External-beam radiation therapy (RT) is standard of care (SOC) for pain relief of symptomatic bone metastases. We aimed to evaluate the efficacy of radiation to asymptomatic bone metastases in preventing skeletal-related events (SRE). METHODS: In a multicenter randomized controlled trial, adult patients with widely metastatic solid tumor malignancies were stratified by histology and planned SOC (systemic therapy or observation) and randomly assigned in a 1:1 ratio to receive RT to asymptomatic high-risk bone metastases or SOC alone. The primary outcome of the trial was SRE. Secondary outcomes included hospitalizations for SRE and overall survival (OS). RESULTS: A total of 78 patients with 122 high-risk bone metastases were enrolled between May 8, 2018, and August 9, 2021, at three institutions across an affiliated cancer network in the United States. Seventy-three patients were evaluable for the primary end point. The most common primary cancer types were lung (27%), breast (24%), and prostate (22%). At 1 year, SRE occurred in one of 62 bone metastases (1.6%) in the RT arm and 14 of 49 bone metastases (29%) in the SOC arm (P < .001). There were significantly fewer patients hospitalized for SRE in the RT arm compared with the SOC arm (0 v 4, P = .045). At a median follow-up of 2.5 years, OS was significantly longer in the RT arm (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.89; P = .018), which persisted on multivariable Cox regression analysis (HR, 0.46; 95% CI, 0.23 to 0.85; P = .01). CONCLUSION: Radiation delivered prophylactically to asymptomatic, high-risk bone metastases reduced SRE and hospitalizations. We also observed an improvement in OS with prophylactic radiation, although a confirmatory phase III trial is warranted.

Implementation Strategies to Promote Short-Course Radiation for Bone Metastases.

Importance: For patients with nonspine bone metastases, short-course radiotherapy (RT) can reduce patient burden without sacrificing clinical benefit. However, there is great variation in uptake of short-course RT across practice settings. Objective: To evaluate whether a set of 3 implementation strategies facilitates increased adoption of a consensus recommendation to treat nonspine bone metastases with short-course RT (ie, ≤5 fractions). Design, Setting, and Participants: This prospective, stepped-wedge, cluster randomized quality improvement study was conducted at 3 community-based cancer centers within an existing academic-community partnership. Rollout was initiated in 3-month increments between October 2021 and May 2022. Participants included treating physicians and patients receiving RT for nonspine bone metastases. Data analysis was performed from October 2022 to May 2023. Exposures: Three implementation strategies-(1) dissemination of published consensus guidelines, (2) personalized audit-and-feedback reports, and (3) an email-based electronic consultation platform (eConsult)-were rolled out to physicians. Main Outcomes and Measures: The primary outcome was adherence to the consensus recommendation of short-course RT for nonspine bone metastases. Mixed-effects logistic regression at the bone metastasis level was used to model associations between the exposure of physicians to the set of strategies (preimplementation vs postimplementation) and short-course RT, while accounting for patient and physician characteristics and calendar time, with a random effect for physician. Physician surveys were administered before implementation and after implementation to assess feasibility, acceptability, and appropriateness of each strategy. Results: Forty-five physicians treated 714 patients (median [IQR] age at treatment start, 67 [59-75] years; 343 women [48%]) with 838 unique nonspine bone metastases during the study period. Implementing the set of strategies was not associated with use of short-course RT (odds ratio, 0.78; 95% CI, 0.45-1.34; P = .40), with unadjusted adherence rates of 53% (444 lesions) preimplementation vs 56% (469 lesions) postimplementation; however, the adjusted odds of adherence increased with calendar time (odds ratio, 1.68; 95% CI, 1.20-2.36; P = .003). All 3 implementation strategies were perceived as being feasible, acceptable, and appropriate; only the perception of audit-and-feedback appropriateness changed before vs after implementation (19 of 29 physicians [66%] vs 27 of 30 physicians [90%]; P = .03, Fisher exact test), with 20 physicians (67%) preferring reports quarterly. Conclusions and Relevance: In this quality improvement study, a multicomponent set of implementation strategies was not associated with increased use of short-course RT within an academic-community partnership. However, practice improved with time, perhaps owing to secular trends or physician awareness of the study. Audit-and-feedback was more appropriate than anticipated. Findings support the need to investigate optimal approaches for promoting evidence-based radiation practice across settings.

Durable Complete Remission With Combination of Stereotactic Body Radiation Therapy (SBRT) and Talimogene Laherparepvec (TVEC) Followed by Ipilimumab in Refractory Metastatic Melanoma.

Metastatic melanoma refractory to checkpoint inhibitors is a challenging clinical scenario. We present the case of a patient who was refractory to standard of care but was able to achieve a durable complete remission with the combination of stereotactic body radiation therapy (SBRT), talimogene laherparepvec (TVEC), and ipilimumab.

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment.

Multidisciplinary Treatment of Non-Spine Bone Metastases: Results of a Modified Delphi Consensus Process.

Purpose: Local treatment for bone metastases is becoming increasingly complex. National guidelines traditionally focus only on radiation therapy (RT), leaving a gap in clinical decision support resources available to clinicians. The objective of this study was to reach expert consensus regarding multidisciplinary management of non-spine bone metastases, which would facilitate standardizing treatment within an academic-community partnership. Methods and Materials: A multidisciplinary panel of physicians treating metastatic disease across the Memorial Sloan Kettering (MSK) Cancer Alliance, including community-based partner sites, was convened. Clinical questions rated of high importance in the management of non-spine bone metastases were identified via survey. A literature review was conducted, and panel physicians drafted initial recommendation statements. Consensus was gathered on recommendation statements through a modified Delphi process from a full panel of 17 physicians from radiation oncology, orthopaedic surgery, medical oncology, interventional radiology, and anesthesia pain. Consensus was defined a priori as 75% of respondents indicating "agree" or "strongly agree" with the consensus statement. Strength of Recommendation Taxonomy was employed to assign evidence strength for each statement. Results: Seventeen clinical questions were identified, of which 11 (65%) were selected for the consensus process. Consensus was reached for 16 of 17 answer statements (94%), of which 12 were approved after Round 1 and additional 4 approved after Round 2 of the modified Delphi voting process. Topics included indications for referral to surgery or interventional radiology, radiation fractionation and appropriate use of stereotactic approaches, and the handling of systemic therapies during radiation. Evidence strength was most commonly C (n = 7), followed by B (n = 5) and A (n = 3). Conclusions: Consensus among a multidisciplinary panel of community and academic physicians treating non-spine bone metastases was feasible. Recommendations will assist clinicians and potentially provide measures to reduce variation across diverse practice settings. Findings highlight areas for further research such as pathologic fracture risk estimation, pre-operative radiation, and percutaneous ablation.

Fibroblast Growth Factor Receptor 3 Amplified Metastatic Melanoma Treated With Erdafitinib.

The treatment of metastatic melanoma has changed dramatically in the last decade with the introduction of immunotherapy and targeted therapy. A futile disease in the past is now treated with various options, resulting in improvement in progression-free and overall survivals, along with improvement in the quality of life. Having said that, the majority of patients with metastatic melanoma eventually succumb to the disease. Molecular profiling of each tumor in the advanced stage is standard of care now, as this would lead to individualized treatment options for each patient. Here, we present a rare case of fibroblast growth factor receptor 3 (FGFR 3) amplified metastatic melanoma, treated rather unconventionally with FGFR 3 inhibitor erdafitinib.

Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

Evaluation of coplanar partial left breast irradiation using tomotherapy-based topotherapy.

PURPOSE: To investigate the use of topotherapy for accelerated partial breast irradiation through field-design optimization and dosimetric comparison to linear accelerator-based three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Hypothetical 3-cm lumpectomy sites were contoured in each quadrant of a left breast by using dosimetric guidelines from the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol. Coplanar intensity-modulated topotherapy treatment plans were optimized by using two-, three-, four-, five-, and seven-field arrangements for delivery by the tomotherapy unit with fixed gantry angles. Optimized noncoplanar five-field 3D-CRT and IMRT were compared with corresponding topotherapy plans. RESULTS: On average, 99.5% +/- 0.5% of the target received 100% of the prescribed dose for all topotherapy plans. Average equivalent uniform doses ranged from 1.20-2.06, 0.79-1.76, and 0.10-0.29 Gy for heart, ipsilateral lung, and contralateral lung, respectively. Average volume of normal breast exceeding 90% of the prescription and average area of skin exceeding 35 Gy were lowest for five-field plans. Average uniformity indexes for five-field plans using 3D-CRT, IMRT, and topotherapy were 1.047, 1.050, and 1.040, respectively. Dose-volume histograms and calculated equivalent uniform doses of all three techniques illustrate clinically equivalent doses to ipsilateral breast, lung, and heart. CONCLUSIONS: This dosimetric evaluation for a single patient shows that coplanar partial breast topotherapy provides good target coverage with exceptionally low dose to organs at risk. Use of more than five fields provided no additional dosimetric advantage. A comparison of five-field topotherapy to 3D-CRT and IMRT for accelerated partial breast irradiation illustrates equivalent target conformality and uniformity.

Computed tomography-based anatomic assessment overestimates local tumor recurrence in patients with mass-like consolidation after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

PURPOSE: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. METHODS AND MATERIALS: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. RESULTS: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade ≥ 2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). CONCLUSION: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT.

Quantifying the reproducibility of heart position during treatment and corresponding delivered heart dose in voluntary deep inhalation breath hold for left breast cancer patients treated with external beam radiotherapy.

PURPOSE: Voluntary deep inhalation breath hold (VDIBH) reduces heart dose during left breast irradiation. We present results of the first study performed to quantify reproducibility of breath hold using bony anatomy, heart position, and heart dose for VDIBH patients at treatment table. METHODS AND MATERIALS: Data from 10 left breast cancer patients undergoing VDIBH whole-breast irradiation were analyzed. Two computed tomography (CT) scans, free breathing (FB) and VDIBH, were acquired to compare dose to critical structures. Pretreatment weekly kV orthogonal images and tangential ports were acquired. The displacement difference from spinal cord to sternum across the isocenter between coregistered planning Digitally Reconstructed Radiographs (DRRs) and kV imaging of bony thorax is a measure of breath hold reproducibility. The difference between bony coregistration and heart coregistration was the measured heart shift if the patient is aligned to bony anatomy. RESULTS: Percentage of dose reductions from FB to VDIBH: mean heart dose (48%, SD 19%, p = 0.002), mean LAD dose (43%, SD 19%, p = 0.008), and maximum left anterior descending (LAD) dose (60%, SD 22%, p = 0.008). Average breath hold reproducibility using bony anatomy across the isocenter along the anteroposterior (AP) plane from planning to treatment is 1 (range, 0-3; SD, 1) mm. Average heart shifts with respect to bony anatomy between different breath holds are 2 ± 3 mm inferior, 1 ± 2 mm right, and 1 ± 3 mm posterior. Percentage dose changes from planning to delivery: mean heart dose (7%, SD 6%); mean LAD dose, ((9%, SD 7%)S, and maximum LAD dose, (11%, SD 11%) SD 11%, p = 0.008). CONCLUSION: We observed excellent three-dimensional bony registration between planning and pretreatment imaging. Reduced delivered dose to heart and LAD is maintained throughout VDIBH treatment.

Use of megavoltage computed tomography with image registration for high-dose rate treatment planning of an oral tongue cancer using a custom oral mold applicator with embedded lead shielding.

PURPOSE: A patient with a lateral oral tongue cancer was treated with high-dose rate brachytherapy using an oral applicator with embedded lead shielding making conventional simulation, using either kilovoltage computed tomography or radiographs, impossible because of scatter artifact. METHODS AND MATERIALS: Treatment simulation was accomplished using megavoltage computed tomography (MVCT) simulation on a helical tomotherapy unit. Because of difficulty in visualization of the catheters on the patient MVCT images, Velocity AI image registration software (Velocity Medical Solutions, Atlanta, GA) was used to register an MVCT of the applicator itself with the patient MVCT simulation. The treatment plan was manually optimized to prescribe 4Gy/fraction to the gross tumor volume. RESULTS: The patient tolerated the treatment well, with no evidence of disease 6 months after treatment. Thermoluminescent dosimeter measurements showed that the shielding reduced the dose by up to 90%, depending on the location of the thermoluminescent dosimeter. While the patient was treated using dose distributions calculated in a homogeneous medium (Task Group-43), an approximation of the true dose distributions was retrospectively calculated using Acuros (Varian Medical Systems Inc., Palo Alto, CA), which accounts for heterogeneities in the patient. DISCUSSION: Use of the MVCT with image registration allowed treatment planning in the presence of lead shielding. Dose-volume histograms showed that recalculation of the dose using heterogeneity correction did not affect the dose to the gross tumor volume, but that the dose to normal structures (maxilla and mandible) was reduced by the lead shielding. CONCLUSION: The use of MVCT and image registration allows for optimized planning in the presence of shielding, which would not be possible with conventional kilovoltage computed tomography.

Helical tomotherapy simultaneous integrated boost provides a dosimetric advantage in the treatment of primary intracranial tumors.

OBJECTIVE: The research quantitatively evaluates the dosimetric advantage of a helical tomotherapy (HT) intensity-modulated radiation therapy simultaneous integrated boost (SIB) compared to a conventional HT sequential (SEQ) boost for primary intracranial tumors. METHODS: Hypothetical lesions (planning target volumes or PTVs) were contoured within computed tomography scans from normal controls. A dose of 50 Gy was prescribed to the larger PTV1, while the boost PTV2 received a total of 60 Gy. HT SEQ and HT SIB plans were generated and compared. We evaluated the mean brain dose, the volume of normal brain receiving 45 Gy (V45), the volume of normal brain receiving 5 Gy (V5), and the integral dose. In addition, patients who were treated with the HT SEQ technique were replanned with the HT SIB technique and compared. RESULTS: The average reduction in mean brain dose with the HT SIB plan compared to the composite HT SEQ plan was 11·0% [standard error (SE): 0·5]. The reductions in brains V45 and V5 were 43·7% (SE: 2·3) and 3·9% (SE: 0·6), respectively. The reduction in the integral dose was 11·0% (SE: 0·5). When comparing the SIB plan to the first 50 Gy only of the SEQ plan, there was only a 2·5% increase in the mean brain dose and a 2·9% increase in brain V45. This increase was dependent on the relative volumes of PTV2 and PTV1. These results were confirmed for the patient plans compared. CONCLUSIONS: Treating primary brain tumors with the HT SIB technique provides significant sparing of normal brain parenchyma compared to a conventional HT SEQ boost.

Helical tomotherapy-based STAT RT: Dosimetric evaluation for clinical implementation of a rapid radiation palliation program.

Helical tomotherapy-based STAT radiation therapy (RT) uses an efficient software algorithm for rapid intensity-modulated treatment planning, enabling conformal radiation treatment plans to be generated on megavoltage computed tomography (MVCT) scans for CT simulation, treatment planning, and treatment delivery in one session. We compared helical tomotherapy-based STAT RT dosimetry with standard linac-based 3D conformal plans and standard helical tomotherapy-based intensity-modulated radiation therapy (IMRT) dosimetry for palliative treatments of whole brain, a central obstructive lung mass, multilevel spine disease, and a hip metastasis. Specifically, we compared the conformality, homogeneity, and dose with regional organs at risk (OARs) for each plan as an initial step in the clinical implementation of a STAT RT rapid radiation palliation program. Hypothetical planning target volumes (PTVs) were contoured on an anthropomorphic phantom in the lung, spine, brain, and hip. Treatment plans were created using three planning techniques: 3D conformal on Pinnacle³, helical tomotherapy, and helical tomotherapy-based STAT RT. Plan homogeneity, conformality, and dose to OARs were analyzed and compared. STAT RT and tomotherapy improved conformality indices for spine and lung plans (CI spine = 1.21, 1.17; CI lung = 1.20, 1.07, respectively) in comparison with standard palliative anteroposterior/posteroanterior (AP/PA) treatment plans (CI spine = 7.01, CI lung = 7.30), with better sparing of heart, esophagus, and spinal cord. For palliative whole-brain radiotherapy, STAT RT and tomotherapy reduced maximum and mean doses to the orbits and lens (maximum/mean lens dose: STAT RT = 2.94/2.65 Gy, tomotherapy = 3.13/2.80 Gy, Lateral opposed fields = 7.02/3.65 Gy), with an increased dose to the scalp (mean scalp dose: STAT RT = 16.19 Gy, tomotherapy = 15.61 Gy, lateral opposed fields = 14.01 Gy). For bony metastatic hip lesions, conformality with both tomotherapy techniques (CI = 1.01 each) is superior to AP/PA treatments (CI = 1.21), as expected. Helical tomotherapy-based STAT RT treatment planning provides clinically acceptable dosimetry, with conformality and homogeneity that is superior to standard linac-based 3D conformal planning and is only slightly inferior to standard helical tomotherapy IMRT dosimetry. STAT RT facilitates rapid treatment planning and delivery for palliative radiation of patients with metastatic disease, with relative sparing of adjacent OARs compared with standard 3D conformal plans.

Helical tomotherapy-based STAT stereotactic body radiation therapy: Dosimetric evaluation for a real-time SBRT treatment planning and delivery program.

Stereotactic body radiation therapy (SBRT) treatments have high-dose gradients and even slight patient misalignment from the simulation to treatment could lead to target underdosing or organ at risk (OAR) overdosing. Daily real-time SBRT treatment planning could minimize the risk of geographic miss. As an initial step toward determining the clinical feasibility of developing real-time SBRT treatment planning, we determined the calculation time of helical TomoTherapy-based STAT radiation therapy (RT) treatment plans for simple liver, lung, and spine SBRT treatments to assess whether the planning process was fast enough for practical clinical implementation. Representative SBRT planning target volumes for hypothetical liver, peripheral lung, and thoracic spine lesions and adjacent OARs were contoured onto a planning computed tomography scan (CT) of an anthropomorphic phantom. Treatment plans were generated using both STAT RT "full scatter" and conventional helical TomoTherapy "beamlet" algorithms. Optimized plans were compared with respect to conformality index (CI), heterogeneity index (HI), and maximum dose to regional OARs to determine clinical equivalence and the number of required STAT RT optimization iterations and calculation times were determined. The liver and lung dosimetry for the STAT RT and standard planning algorithms were clinically and statistically equivalent. For the liver lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.04 and 1.04 and HI of 1.03 and 1.03, respectively. For the lung lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.05 and 1.03 and HI of 1.05and 1.05, respectively. For spine lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.15 and 1.14 and HI of 1.22 and 1.14, respectively. There was no difference between treatment algorithms with respect to maximum doses to the OARs. The STAT RT iteration time with current treatment planning systems is 45 sec, and the treatment planning required 3 iterations or 135 sec for STAT RT liver and lung SBRT plans and 7 iterations or 315 sec for STAT RT spine SBRT plans. Helical TomoTherapy-based STAT RT treatment planning with the "full scatter" algorithm provides levels of dosimetric conformality, heterogeneity, and OAR avoidance for SBRT treatments that are clinically equivalent to those generated with the Helical TomoTherapy "beamlet" algorithm. STAT RT calculation times for simple SBRT treatments are fast enough to warrant further investigation into their potential incorporation into an SBRT program with daily real-time planning. Development of methods for accurate target and OAR determination on megavoltage computed tomography scans incorporating high-resolution diagnostic image co-registration software and CT detector-based exit dose measurement for quality assurance are necessary to build a real-time SBRT planning and delivery program.

Accelerated treatment using intensity-modulated radiation therapy plus concurrent capecitabine for unresectable hepatocellular carcinoma.

BACKGROUND: : Patients with unresectable hepatocellular carcinoma (HCC) have limited treatment options. In this study, the authors investigated the feasibility, toxicity, and efficacy associated with intensity-modulated radiation therapy (IMRT) and concurrent, chronomodulated capecitabine in the treatment of unresectable HCC. METHODS: : Twenty patients underwent treatment planning for HCC confined to the liver with helical tomotherapy-based IMRT. Fifty-five percent of patients had Child-Pugh Class A disease, and 45% of patients had Class B disease. Ninety-five percent of patients were prescribed 50 gray (Gy) of radiotherapy to the planning target volume delivered in 20 fractions with concurrent, chronomodulated capecitabine. Transcatheter arterial chemoembolization preceded radiotherapy in 11 patients, and 9 patients received IMRT alone because of portal vein thrombosis, esophageal varices, or tumor size. RESULTS: : The mean greatest tumor dimension was 9 cm (range, 1.3-17.4 cm), the mean dose to normal liver was 22.6 Gy (range, 10-29.2 Gy), and the average volume of liver that received >30 Gy (V30) was 27.2% (range, 12%-43%). Eighteen patients (90%) completed the prescribed treatment of 50 Gy. There was no increase from baseline in acute or late toxicity greater than 2 grades. Partial response or disease stability was achieved at 3 months to 6 months after treatment in 15 of 16 patients (94%). The median survival (+/-standard deviation) for patients who had Child-Pugh Class A and B disease was 22.5 +/- 5.1 months and 8 +/- 3.3 months, respectively. CONCLUSIONS: : In this initial experience with accelerated IMRT plus capecitabine for patients who had large HCC lesions, the results demonstrated acceptable toxicity with promising local control. The relatively low acute and late toxicity observed with this program suggested that dose intensification can be incorporated into the treatment regimen if needed. Cancer 2009. (c) 2009 American Cancer Society.

Recurrence rates and analysis of close or positive margins in patients treated without re-excision before radiation for breast cancer.

PURPOSE: This study examines the risk of local recurrence in a group of patients accepted for radiation therapy after breast-conserving surgery despite having a close or positive resection margin. METHODS AND MATERIALS: Two hundred patients with early-stage breast cancer were treated by radiation with a nonnegative margin < or =2 mm from January 1974 to September 2001. The median age was 61 years. Margins were positive in 29% and close (< or =2 mm) in 71%. The median dose was 64 to 66 Gy. The median follow up was 5.9 years. RESULTS: The number of resection margins close or positive was 1 in 73% of patients, 2 in 14%, 3 in 1%, and unknown in 12%. The margin location was 23% anterior, 24% posterior, 12% medial, 12% lateral, 17% superior, and 12% inferior. Reasons for not reexcising were advanced age/comorbidities in 7%, anterior location under skin in 25%, posterior location to muscle in 15%, focal involvement in 13%, no extensive intraductal component in 5%, surgeon refusal in 15%, and patient refusal in 20%. There was a strong association between an anterior or posterior margin location and the rationale of no additional breast tissue at the margin to reexcise before radiation. The risk of local recurrence at 5 and 10 years was 3% and 5%, respectively. CONCLUSIONS: Further research of close and positive margins is needed to validate features identified in this series, particularly nonbreast tissue anatomic margins, that are associated with low risks of local recurrence after radiation.