The Role of Axillary Lymph Node Dissection versus Sentinel Lymph Node Dissection in Breast Cancer Patients with Clinical N2b-N3c Disease Who Receive Adjuvant Radiotherapy.

BACKGROUND: For breast cancer with advanced regional lymph node involvement, axillary lymph node dissection (ALND) remains the standard of care for staging and treating the axilla despite the presence of undissected lymph nodes. The benefit of ALND in this setting is unknown. OBJECTIVES: We sought to describe national patterns of care of axillary surgery and its association with overall survival (OS) among women with cN2b-N3c breast cancer who receive adjuvant radiotherapy. PATIENTS AND METHODS: We identified female patients with cN2b-N3c breast cancer from 2012 to 2017 from the National Cancer Database. Clinical and demographic information were analyzed using Wilcoxon rank sum and χ2 tests. Predictors of receipt of ALND and predictors of death were identified with multivariable logistic regression modeling. Inverse probability of treatment weighting was implemented to adjust for differences in treatment cohorts. The Kaplan-Meier method was used to evaluate OS. RESULTS: We identified 7167 patients. Of these, 922 (13%) received SLNB and 6254 (87%) received ALND; 7% were cN2b, 19% cN3a, 24% cN3b, 19% cN3c, and 31% cN3, not otherwise specified. Predictors of receipt of ALND were age 50-69 years [odds ratio (OR) 1.3, p < 0.01], cN3a (OR 7.6, p < 0.01), cN3b (OR 2.8, p < 0.01), and cN3c (OR 4.2, p < 0.01). Predictors of death included cN3c (OR 1.9, p < 0.01), age 70-90 years (OR 1.5, p = 0.01), and positive surgical margins (OR 1.5, p < 0.01). After cohort balancing, ALND was not associated with improved OS when compared with SLNB (HR 0.99, p = 0.91). CONCLUSIONS: ALND in patients with advanced nodal disease was not associated with improved survival compared with SLNB for women who receive adjuvant radiotherapy.

Surgeon-Level Variation in Utilization of Local Staging and Neoadjuvant Therapy for Stage II-III Rectal Adenocarcinoma.

INTRODUCTION: Neoadjuvant therapy (NT) is the standard of care for clinical stage II-III rectal adenocarcinoma, but utilization remains suboptimal. We aimed to determine the underlying reasons for omission of local staging and NT. METHODS: We conducted a retrospective study of patients with clinical stage II-III or undocumented clinical stage/pathologic stage II-III rectal adenocarcinoma who were treated in 2010-2016 in one of nine Intermountain Healthcare hospitals. The outcomes of omission of local staging and NT were examined with multivariable models. Risk- and reliability-adjusted rates of local staging and NT were calculated for surgeons who treated ≥ 3 patients. Pathologic and long-term outcomes were examined after excluding patients who were not resected or who underwent local excision (N = 11). RESULTS: Local staging was omitted in 43/240 (17.9%) patients and NT was omitted in 41/240 (17.1%). The strongest risk factors for local staging and NT omission were upper rectal tumors and surgeons who treated ≤ 3 cases/year. Thirty-six of 41 (87.8%) cases of omitted NT had local staging omitted. Adjusted surgeon-specific local staging rates varied 1.6-fold (56.3-92.4%) and NT rates varied 2.8-fold (34.1-97.1%). Surgeon local staging and NT rates were strongly correlated (r = 0.92). NT was associated with lower rates of positive circumferential radial margins (7.9 vs. 20.0%; P = 0.02), node positivity (33.3 vs. 55.0%; P = 0.01), and local recurrences (7.6 vs. 14.9% at 5 years; P = 0.0176). CONCLUSIONS: NT omission should be understood as a consequence of surgeon failure to perform local staging in most cases. Quality improvement efforts should focus on improving utilization of local staging.

Value of surgical resection and timing of therapy in patients with pancreatic cancer at high risk for positive margins.

BACKGROUND: Surgical resection remains the best chance at long-term survival in pancreatic cancer, though margin-positive resections are associated with diminished survival. We examined the effect of margin-positive resection on survival, as well as the role and timing of additional therapies through the National Cancer Database (NCDB). PATIENTS AND METHODS: Patients with stage IIA-III pancreatic adenocarcinoma diagnosed from 2004 to 2013 were identified in NCDB. Survival was compared using univariate and multivariate Cox proportional hazards modelling for patients who underwent surgery with negative (R0), microscopically positive (R1) and macroscopically positive (R2) margins or non-surgical treatment. We further analysed patients by margin status, timing of additional therapy (neoadjuvant therapy (NAT) vs adjuvant therapy (AT) vs none) and clinical stage. RESULTS: We analysed 44 852 patients. Median survival (MS) for patients who did not undergo surgery was 10.3 months, compared with 19.7 months for R0 (P<0.001), 14.3 months for R1 (P<0.001) and 9.8 months (P=0.07) for R2 resections. NAT (MS 23.2 months) was associated with improved survival compared with AT (MS 21.5 months) in negative-margin patients and equivalent (MS 17.6 months) to AT (MS 16.8 months) in positive-margin patients. Survival for stage III NAT positive-margin patients (MS 19.8 months) was equivalent to AT after negative margins (MS 18.4 months, P=1.00). Improved R0 rates were seen with NAT (88% vs 81%, P<0.001), especially in stage III patients (85% vs 59%, P<0.001). CONCLUSION: R1 resections portend poorer survival than R0 but do not negate the benefit of surgery when additional therapy is given. NAT was associated with improved R0 rates and improved survival for stage III positive-margin patients.

Vulvar Recurrences After Intensity-modulated Radiation Therapy for Squamous Cell Carcinoma of the Anus.

OBJECTIVES: The objective is to determine localregional control (LRC), distant metastasis free survival, disease-free survival, overall survival (OS), and toxicity for patients with squamous cell carcinoma of the anus treated with definitive chemotherapy and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: We conducted a retrospective review of patients treated using IMRT for squamous cell carcinoma of the anus at our institution since 2005. Patients with local recurrences were identified and reviewed. The Kaplan-Meier curves were used for LRC and OS. RESULTS: From 2005 to 2014, 52 patients were treated with IMRT-based chemoradiation for squamous cell carcinoma of the anus. Median dose to the primary tumor was 54 Gy. LRC, distant metastasis free survival, OS, and disease-free survival were 92.3%, 88.5%, 86.5%, and 84.6%, respectively, with a median follow-up of 20 months. Two local failures occurred at the anal primary site and 2 in the vulva. Despite subsequent palliative radiotherapy and chemotherapy, neither patient with a vulvar recurrence achieved disease control. CONCLUSIONS: In a cohort of patients treated with IMRT-based chemoradiation, 2 vulvar recurrences were identified within the avoided external genitalia despite limited recurrence rates within the cohort overall. This experience suggests that for patients with a locally advanced primary tumor and bulky bilateral inguinal or pelvic disease, the in-transit vulvar dermal lymphatics may be at risk for subclinical involvement and subsequent recurrence. If substantiated by a similar pattern of recurrence at other institutions, the external genitalia may need to be reclassified from an avoidance structure to a clinical treatment volume in patients with locally advanced anal cancer.

Is radiation indicated for young women with early stage, node-negative breast cancer after mastectomy? A multi-institution, retrospective review.

The role of post-mastectomy radiation for women with node negative, early stage disease is not well-defined. The purpose of this study is to more clearly define a subset of women who are ≤40 years of age with T1-T2, node negative breast cancer who may benefit from post-mastectomy radiation. Using tumor registries at two institutions, we identified 219 women ≤40 years of age with T1-T2, node negative breast cancer treated with mastectomy. Of these 219 patients, 38 received post-mastectomy radiation and 181 did not. Kaplan-Meier methods and cox proportional-hazards regression models were employed for statistical analysis. There were no locoregional failures in the women receiving post mastectomy radiation, which lead to a nonsignificant increase in freedom from locoregional recurrence (P=.08). For women not receiving post-mastectomy radiation, freedom from locoregional recurrence was 94.7% and 89.7% at 5- and 10-years. Lymphovascular space invasion (LVSI) was the only factor predictive of locoregional recurrence. For women without LVSI, freedom from locoregional recurrence was 96.0% and 93.3% at 5- and 10-years respectively. For women with LVSI who did not receive post mastectomy radiation, freedom from locoregional recurrence was 89.1% at 5-years. There were no failures in the women with LVSI who received post mastectomy radiation. For women ≤40 years of age with T1-2, node negative breast cancer treated with mastectomy and no post-mastectomy radiation, locoregional control is excellent in the absence of LVSI, regardless of other risk factors. In the presence of LVSI (regardless of other risk factors), the risk of locoregional recurrence is high and appears to be decreased with post-mastectomy radiation.

Chemoradiation Therapy for Unresected Extrahepatic Cholangiocarcinoma: A Propensity Score-Matched Analysis.

BACKGROUND: Unresected extrahepatic cholangiocarcinoma (uEHCC) remains a deadly disease. Guidelines for uEHCC recommend either chemotherapy alone (CT) or chemoradiotherapy (CRT). This study used the National Cancer Database (NCDB) to compare outcomes for patients treated with CT and those who underwent CRT. METHODS: Patients with initially diagnosed non-metastatic uEHCC from 2004 to 2014 were identified. Using Chi square analysis, patients who underwent CT were compared with those who received CRT. Uni- and multivariate Cox regression analyses were used to compare characteristics related to survival. Propensity score matching and shared frailty analysis were undertaken to correct for baseline differences between the two groups. Additional analyses were performed to compare survival for the minority of patients who underwent surgery and advanced-stage patients. RESULTS: The study identified 2996 patients with uEHCC. Chemoradiation was associated with better survival (median survival [MS], 14.5 months; hazard ratio [HR] 0.84; p < 0.001) than CT alone (MS, 12.6 months). Induction of CT before CRT was associated with a trend toward decreased risk of death compared with concurrent CRT (HR 0.81; p = 0.051). For the patients able to undergo surgery after initial treatment, MS was 24.5 months (HR 0.38; p < 0.001) versus 12.2 months for those who had no surgery. For these patients, CRT also was associated with better survival (MS, 31.2 months; HR 0.66; p = 0.001) than CT (MS, 22.1 months). Positive margins at surgery yielded survival equivalent to that with no surgery. CONCLUSION: Although CRT may be associated with slightly better survival in uEHCC than CT alone, the majority of the benefit was observed for patients able to undergo eventual surgery.

Multiagent induction chemotherapy followed by chemoradiation is associated with improved survival in locally advanced pancreatic cancer.

BACKGROUND: The role of chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) is uncertain after multiple randomized clinical trials have yielded mixed results. The authors used the National Cancer Data Base (NCDB) to determine whether CRT yields a survival benefit compared with chemotherapy alone (CT). METHODS: Patients with nonmetastatic LAPC diagnosed during 2004 through 2014 were identified in the NCDB. Patients who received CT were compared with those who received CRT using chi-square analysis. Univariate and multivariate Cox regression analyses were used to compare demographic, clinical, and treatment characteristics that were predictive of survival. Propensity score matching and shared frailty analysis were done. Subgroup analyses were undertaken to examine patients who underwent pancreatectomy and cohorts of patients who received different CT or CRT regimens. RESULTS: In total, 8689 patients with LAPC were identified. CRT was associated with improved survival (median survival [MS], 13.5 months) compared with CT (MS, 10.6 months) on multivariate analysis (hazard ratio [HR], 0.80; P < .001). Induction chemotherapy before CRT (HR, 0.67; P < .001) and multiagent chemotherapy (HR, 0.72; P < .001) were also identified as independent predictors of survival compared with concurrent CRT and single-agent CT, respectively. Patients in the CRT group who received multiagent induction chemotherapy had superior MS and pancreatectomy rates (MS, 17.5 months; HR, 0.70; P < .001; pancreatectomy rate, 10%) compared with those who received multiagent CT alone (MS, 12.4 months; pancreatectomy rate, 3.3%). Patients who underwent pancreatectomy experienced improved survival (MS, 22 vs 10.6 months; HR, 0.39; P < .001). CONCLUSIONS: In this NCDB analysis, maximizing systemic chemotherapy before CRT improved survival compared with CT alone in patients with LAPC. Continued analysis of CRT in properly selected patients after maximized systemic therapy is needed. Cancer 2017;123:3816-24. © 2017 American Cancer Society.

Differences in Parotid Dosimetry and Expected Normal Tissue Complication Probabilities in Whole Brain Radiation Plans Covering C1 Versus C2.

OBJECTIVES: There is no consensus standard regarding the placement of the inferior field border in whole brain radiation therapy (WBRT) plans, with most providers choosing to cover the first versus (vs.) second cervical vertebrae (C1 vs. C2). We hypothesize that extending coverage to C2 may increase predicted rates of xerostomia. METHODS: Fifteen patients underwent computed tomography (CT) simulation; two WBRT plans were then produced, one covering C2 and the other covering C1. The plans were otherwise standard, and patients were prescribed doses of 25, 30 and 37.5 gray (Gy). Dose-volume statistics were obtained and normal tissue complication probabilities (NTCPs) were estimated using the Lyman-Burman-Kutcher model. Mean parotid dose and predicted xerostomia rates were compared for plans covering C2 vs. C1 using a two-sided patient-matched t-test. Plans were also evaluated to determine whether extending the lower field border to cover C2 would result in a violation of commonly accepted dosimetric planning constraints. RESULTS: The mean dose to both parotid glands was significantly higher in WBRT plans covering C2 compared to plans covering C1 for all dose prescriptions (p<0.01). Normal tissue complication probabilities were also significantly higher when covering C2 vs. C1, for all prescribed doses (p<0.01). Predicted median rates of xerostomia ranged from <0.03%-21% for plans covering C2 vs. <0.001%-12% for patients treated with plans covering C1 (p<0.01), dependent on the treatment dose and NTCP model. Plans covering C2 were unable to constrain at least one parotid to <20 Gy in 31% of plans vs. 9% of plans when C1 was covered. A total parotid dose constraint of <25 Gy was violated in 13% of plans covering C2 vs. 0% of plans covering C1. CONCLUSIONS: Coverage of C2 significantly increases the mean parotid dose and predicted NTCPs and results in more frequent violation of commonly accepted dosimetric planning constraints.

Post-mastectomy Radiotherapy for pT3N0 Breast Cancers: A Retrospective, Multi-Institution Review.

The role of post-mastectomy radiotherapy for pT3N0 breast cancers remains undefined. The purpose of this study was to report institutional outcomes for women with pT3N0 breast cancers treated with and without post-mastectomy radiotherapy. We collected data from two large tumor registries on pT3N0 breast cancers diagnosed between 1985 and 2014. Kaplan-Meier estimates were used to analyze freedom from local-regional recurrence (FFLR), relapse free survival, and overall survival. This analysis identified 93 women with pT3N0 breast cancers. Of these, 53 received post-mastectomy radiotherapy and 40 did not. Median follow-up was 6.2 years and 5.3 years in the non-post-mastectomy radiotherapy and post-mastectomy radiotherapy cohorts, respectively. Women not undergoing post-mastectomy radiotherapy were more likely to be diagnosed in the 1980s and 1990s and were less likely to receive systemic therapies than women receiving post-mastectomy radiotherapy (p < 0.05). There was a trend toward increased FFLR in the women receiving post-mastectomy radiotherapy (p = 0.15). FFLR in the post-mastectomy radiotherapy cohort was 98% at both 5 and 10 years. For women not receiving post-mastectomy radiotherapy, FFLR was 88% at both 5 and 10 years. Women not receiving post-mastectomy radiotherapy in our study had an isolated local-regional failure rate of 12% at 10 years, despite receiving inferior systemic treatment by current standards. Local-regional control after post-mastectomy radiotherapy for pT3N0 breast cancers was excellent. Further research is needed to define post-mastectomy radiotherapy indications for this patient population when receiving chemotherapy and endocrine therapy in line with current guidelines.

In the Modern Treatment Era, Is Breast Conservation Equivalent to Mastectomy in Women Younger Than 40 Years of Age? A Multi-Institution Study.

PURPOSE: Mastectomy is often recommended for women ≤40 years of age with breast cancer, as young women were under-represented in the landmark trials comparing breast conservation therapy (BCT) to mastectomy. We hypothesized that, in the modern treatment era, BCT and mastectomy result in equivalent local control rates in young women. METHODS AND MATERIALS: Breast cancer cases arising between 1975 and 2013 in women ≤40 years old were collected from the tumor registries of 2 large healthcare systems in Utah. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze freedom from locoregional recurrence (FFLR), overall survival (OS), and relapse-free survival (RFS). RESULTS: This analysis identified 853 BCT candidates. A comparison of BCT to mastectomy after 2000 showed FFLR, RFS, and OS were all similar. Rate for FFLR at 10 years was 94.9% versus 92.1% for BCT and mastectomy, respectively (P=.57). For women whose cancer was diagnosed after 2000, who received BCT, FFLR and RFS rates were improved compared to those whose cancer was diagnosed prior to 2000 (P<.05), whereas OS (P=.46) rates were similar. Among those who underwent mastectomy, FFLR, OS, and RFS were significantly improved (P<.05) with diagnosis after 2000. CONCLUSIONS: FFLR rates for young women, ≤40 years of age, have significantly improved for BCT and mastectomy over time. If patients were treated after 2000, BCT appears to be safe and equivalent to mastectomy at 10 years in terms of FFLR, OS, and RFS.

Rapid Automated Target Segmentation and Tracking on 4D Data without Initial Contours.

Purpose. To achieve rapid automated delineation of gross target volume (GTV) and to quantify changes in volume/position of the target for radiotherapy planning using four-dimensional (4D) CT. Methods and Materials. Novel morphological processing and successive localization (MPSL) algorithms were designed and implemented for achieving autosegmentation. Contours automatically generated using MPSL method were compared with contours generated using state-of-the-art deformable registration methods (using Elastix© and MIMVista software). Metrics such as the Dice similarity coefficient, sensitivity, and positive predictive value (PPV) were analyzed. The target motion tracked using the centroid of the GTV estimated using MPSL method was compared with motion tracked using deformable registration methods. Results. MPSL algorithm segmented the GTV in 4DCT images in 27.0 ± 11.1 seconds per phase (512 × 512 resolution) as compared to 142.3 ± 11.3 seconds per phase for deformable registration based methods in 9 cases. Dice coefficients between MPSL generated GTV contours and manual contours (considered as ground-truth) were 0.865 ± 0.037. In comparison, the Dice coefficients between ground-truth and contours generated using deformable registration based methods were 0.909 ± 0.051. Conclusions. The MPSL method achieved similar segmentation accuracy as compared to state-of-the-art deformable registration based segmentation methods, but with significant reduction in time required for GTV segmentation.

Reirradiation for locoregionally recurrent lung cancer: outcomes in small cell and non-small cell lung carcinoma.

OBJECTIVES: To our knowledge this is the largest report analyzing outcomes for re-irradiation (reRT) for locoregionally recurrent lung cancer, and the first to assess thoracic reRT outcomes in patients with small cell lung cancer (SCLC). METHODS: Forty-eight patients (11 SCLC, 37 non-small cell lung cancer [NSCLC]) receiving reRT to the thorax were identified; 44 (92%) received reRT by intensity-modulated radiotherapy. Palliative responses, survival outcomes, and prognostic factors were analyzed. RESULTS: NSCLC patients received a median of 30 Gy in a median of 10 fractions, whereas SCLC patients received a median of 37.5 Gy in a median of 15 fractions. Median survival for the entire cohort from reRT was 4.2 months. Median survival for NSCLC patients was 5.1 months, versus 3.1 months for the SCLC patients (P=0.15). In NSCLC patients, multivariate analysis demonstrated that Karnofsky performance status≥80 and higher radiation dose were associated with improved survival following reRT, and 75% of patients with symptoms experienced palliative benefit. In SCLC, 4 patients treated with the intent of life prolongation for radiographic recurrence had a median survival of 11.7 months. However, acute toxicities and new disease symptoms limited the duration of palliative benefit in the 7 symptomatic SCLC patients to 0.5 months. CONCLUSIONS: ReRT to the thorax for locoregionally recurrent NSCLC can provide palliative benefit, and a small subset of patients may experience long-term survival. Select SCLC patients may experience meaningful survival prolongation after reRT, but reRT for patients with symptomatic recurrence and/or extrathoracic disease did not offer meaningful survival or durable symptom benefit.

Dose-limiting toxicity after hypofractionated dose-escalated radiotherapy in non-small-cell lung cancer.

PURPOSE: Local failure rates after radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined. PATIENTS AND METHODS: Seventy-nine patients with NSCLC were enrolled on a prospective single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy. Escalation of dose per fraction was performed according to patients' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy. The MTD was defined as the maximum dose with ≤ 20% risk of severe toxicity. RESULTS: No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual. However, with a longer follow-up period, grade 4 to 5 toxicity occurred in six patients and was correlated with total dose (P = .004). An MTD was identified at 63.25 Gy in 25 fractions. Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree. CONCLUSION: Although this dose-escalation model limited the rates of clinically significant pneumonitis, dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures. The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocols, especially when using hypofractionation.

Locoregional recurrence following accelerated partial breast irradiation for early-stage invasive breast cancer: significance of estrogen receptor status and other pathological variables.

BACKGROUND: Understanding risk factors for locoregional recurrence (LRR) after accelerated partial breast irradiation (APBI) can help to guide patient selection for treatment with APBI. Published findings to date have not been consistent. More data are needed as these risk factors continue to be defined. METHODS: A total of 277 women with early-stage invasive breast cancer underwent lumpectomy and were treated adjuvantly at our institution with APBI using high-dose rate brachytherapy. APBI was delivered using multicatheter interstitial brachytherapy (91 %) or single-entry catheter brachytherapy (9 %) to a dose of 32-34 Gy in 8-10 twice daily fractions. Failure patterns and risk factors for recurrence were analyzed. RESULTS: With a median follow-up of 61 months, the 5-year locoregional control rate was 94.4 %. Negative estrogen receptor (ER) status was strongly associated with LRR on multivariate analysis (p < 0.005). Lobular histology, the presence of an extensive intraductal component, and lymphovascular invasion also were significant but to a lesser degree than ER-negative status. Patients with multiple risk factors were at highest risk for LRR. Age was not significantly associated with increased risk for LRR. CONCLUSIONS: The presence of specific pathological features, particularly ER negative status, was associated with increased risk of LRR in this cohort of women treated with APBI. Further investigation is warranted to determine whether patients with adverse pathological risk factors are at higher risk of LRR after APBI than after conventional whole breast irradiation (WBI), as these same features also may place women at risk for LRR after WBI.

Estimated radiation pneumonitis risk after photon versus proton therapy alone or combined with chemotherapy for lung cancer.

BACKGROUND: Traditionally, radiation therapy plans are optimized without consideration of chemotherapy. Here, we model the risk of radiation pneumonitis (RP) in the presence of a possible interaction between chemotherapy and radiation dose distribution. MATERIAL AND METHODS: Three alternative treatment plans are compared in 18 non-small cell lung cancer patients previously treated with helical tomotherapy; the tomotherapy plan, an intensity modulated proton therapy plan (IMPT) and a three dimensional conformal radiotherapy (3D-CRT) plan. All plans are optimized without consideration of the chemotherapy effect. The effect of chemotherapy is modeled as an independent cell killing process using a uniform chemotherapy equivalent radiation dose (CERD) added to the entire organ at risk. We estimate the risk of grade 3 or higher RP (G3RP) using the critical volume model. RESULTS: The mean risk of clinical G3RP at zero CERD is 5% for tomotherapy (range: 1-18 %) and 14% for 3D-CRT (range 2-49%). When the CERD exceeds 9 Gy, however, the risk of RP with the tomotherapy plans become higher than the 3D-CRT plans. The IMPT plans are less toxic both at zero CERD (mean 2%, range 1-5%) and at CERD = 10 Gy (mean 7%, range 1-28%). Tomotherapy yields a lower risk of RP than 3D-CRT for 17/18 patients at zero CERD, but only for 7/18 patients at CERD = 10 Gy. IMPT gives the lowest risk of all plans for 17/18 patients at zero CERD and for all patients with CERD = 10 Gy. CONCLUSIONS: The low dose bath from highly conformal photon techniques may become relevant for lung toxicity when radiation is combined with cytotoxic chemotherapy as shown here. Proton therapy allows highly conformal delivery while minimizing the low dose bath potentially interacting with chemotherapy. Thus, intensive drug-radiation combinations could be an interesting indication for selecting patients for proton therapy. It is likely that the IMRT plans would perform better if the CERD was accounted for during optimization, but more clinical data is required to facilitate evidence-based plan optimization in the multi-modality setting.

Intensity-modulated radiotherapy might increase pneumonitis risk relative to three-dimensional conformal radiotherapy in patients receiving combined chemotherapy and radiotherapy: a modeling study of dose dumping.

PURPOSE: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. METHODS AND MATERIALS: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. RESULTS: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. CONCLUSIONS: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.

Dosimetric comparison of left-sided whole breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and topotherapy.

BACKGROUND AND PURPOSE: To compare left-sided whole breast conventional and intensity-modulated radiotherapy (IMRT) treatment planning techniques. MATERIALS AND METHODS: Treatment plans were created for 10 consecutive patients. Three-dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), and inverse-planned IMRT (inv-IMRT) used two tangent beams. For-IMRT utilized up to four segments per beam. For helical tomotherapy (HT) plans, beamlet entrance and/or exit to critical structures was blocked. Topotherapy plans, which used static gantry angles with simultaneous couch translation and inverse-planned intensity modulation, used two tangent beams. Plans were normalized to 50Gy to 95% of the retracted PTV. RESULTS: Target max doses were reduced with for-IMRT compared to 3DCRT, which were further reduced with HT, topotherapy, and inv-IMRT. HT resulted in lowest heart and ipsilateral lung max doses, but had higher mean doses. Inv-IMRT and topotherapy reduced ipsilateral lung mean and max doses compared to 3DCRT and for-IMRT. CONCLUSIONS: All modalities evaluated provide adequate coverage of the intact breast. HT, topotherapy, and inv-IMRT can reduce high doses to the target and normal tissues, although HT results in increased low doses to large volume of normal tissue. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned modalities.

Outcomes after accelerated partial breast irradiation in patients with ASTRO consensus statement cautionary features.

PURPOSE: To evaluate outcomes among women with American Society for Radiation Oncology (ASTRO) consensus statement cautionary features treated with brachytherapy-based accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: Between March 2001 and June 2006, 322 consecutive patients were treated with high-dose-rate (HDR) APBI at the University of Wisconsin. A total of 136 patients were identified who met the ASTRO cautionary criteria. Thirty-eight (27.9%) patients possessed multiple cautionary factors. All patients received 32 to 34 Gy in 8 to 10 twice-daily fractions using multicatheter (93.4%) or Mammosite balloon (6.6%) brachytherapy. RESULTS: With a median follow-up of 60 months, there were 5 ipsilateral breast tumor recurrences (IBTR), three local, and two loco-regional. The 5-year actuarial rate of IBTR was 4.8%±4.1%. The 5-year disease-free survival was 89.6%, with a cause-specific survival and overall survival of 97.6% and 95.3%, respectively. There were no IBTRs among 32 patients with ductal carcinoma in situ (DCIS) vs. 6.1% for patients with invasive carcinoma (p=0.24). Among 104 patients with Stage I or II invasive carcinoma, the IBTR rate for patients considered cautionary because of age alone was 0% vs. 12.7% in those deemed cautionary due to histopathologic factors (p=0.018). CONCLUSIONS: Overall, we observed few local recurrences among patients with cautionary features. Women with DCIS and patients 50 to 59 years of age with Stage I/II disease who otherwise meet the criteria for suitability appear to be at a low risk of IBTR. Patients with tumor-related cautionary features will benefit from careful patient selection.

Hypofractionation does not increase radiation pneumonitis risk with modern conformal radiation delivery techniques.

PURPOSE: To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models. MATERIAL AND METHODS: Eighteen non-small cell lung cancer patients previously treated with helical tomotherapy were selected. For each patient a 3D-conformal plan (3D-CRT) plan was produced in addition to the delivered plan. The standard fractionation schedule was set to 60 Gy in 30 fractions. Iso-efficacy comparisons with hypofractionation were performed by changing the fractionation and the physical prescription dose while keeping the equivalent tumor dose in 2 Gy fractions constant. The risk of developing RP after radiotherapy was estimated using the Mean Equivalent Lung Dose in 2-Gy fractions (MELD(2)) NTCP model with α/ß=4 Gy for the residual lung. Overall treatment time was kept constant. RESULTS: The mean risk of clinical RP after standard fractionation was 7.6% for Tomotherapy (range: 2.8-15.9%) and 9.2% for 3D-CRT (range 3.2-20.2%). Changing to 20 fractions, the Tomotherapy plans became slightly less toxic if the tumor α/ß ratio, (α/ß)(T), was 7 Gy (mean RP risk 7.5%, range 2.8-16%) while the 3D-CRT plans became marginally more toxic (mean RP risk 9.8%, range 3.2-21%). If (α/ß)(T) was 13 Gy, the mean estimated risk of RP is 7.9% for Tomotherapy (range: 2.8-17%) and 10% for 3D-CRT (range 3.2-22%). CONCLUSION: Modern highly conformal dose distributions are radiobiologically more forgiving with respect to hypofractionation, even for a normal tissue endpoint where α/ß is lower than for the tumor in question.

A solitary seminoma renal metastasis presenting as an incidental renal mass.

A 34-year-old man with an extensive medical history received a CT scan for chronic leg and back pain. Imaging revealed a single, enhancing 8-cm mass in the upper pole of the right kidney. Laparoscopic radical nephrectomy was performed and pathologic finding revealed seminoma. Scrotal ultrasound and subsequent right orchiectomy also revealed seminoma. We discuss the occurrence of renal metastasis in seminoma.