George M. Cannon

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.

Dose Escalated, Hypofractionated Radiotherapy Using Helical Tomotherapy for Inoperable Non-Small Cell Lung Cancer : Preliminary Results of a Risk-Stratified Phase I Dose Escalation Study

To improve local control for inoperable non-small cell lung cancer (NSCLC), a phase I dose escalation study for locally advanced and medically inoperable patients was devised to escalate tumor dose while limiting the dose to organs at risk including the esophagus, spinal cord, and residual lung. Helical tomotherapy provided image-guided IMRT, delivered in a 5-week hypofractionated schedule to minimize the effect of accelerated repopulation. Forty-six patients judged not to be surgical candidates with Stage I-IV NSCLC were treated. Concurrent chemotherapy was not allowed. Radiotherapy was delivered via helical tomotherapy and limited to the primary site and clinically proven or suspicious nodal regions without elective nodal irradiation. Patients were placed in 1 of 5 dose bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. The bin doses of 57 to 80.5 Gy result in 2 Gy/fraction normalized tissue dose (NTD) equivalents of 60 to 100 Gy. In each bin, the starting dose was determined by the relative normalized tissue mean dose modeled to cause < 20% Grade 2 pneumonitis. Dose constraints included spinal cord maximum NTD of 50 Gy, esophageal maximum NTD < 64 Gy to ≤ 0.5 cc volume, and esophageal effective volume of 30%. No grade 3 RTOG acute pneumonitis (NCI-CTC v.3) or esophageal toxicities (CTCAE v.3.0 and RTOG) were observed at median follow-up of 8.1 months. Pneumonitis rates were 70% grade 1 and 13% grade 2. Multivariate analysis identified lung NTDmean (p=0.012) and administration of adjuvant chemotherapy following radiotherapy (p=0.015) to be independent risk factors for grade 2 pneumonitis. Only seven patients (15%) required narcotic analgesics (RTOG grade 2 toxicity) for esophagitis, with only 2.3% average weight loss during treatment. Best in-field gross response rates were 17% complete response, 43% partial response, 26% stable disease, and 6.5% in-field thoracic progression. The out-of-field thoracic failure rate was 13%, and distal failure rate was 28%. The median survival was 18 months with 2-year overall survival of 46.8% ± 9.7% for this cohort, 50% of whom were stage IIIB and 30% stage IIIA. Dose escalation can be safely achieved in NSCLC with lower than expected rates of pneumonitis and esophagitis using hypofractionated image-guided IMRT. The maximum tolerated dose has yet to be reached.

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.

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.

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

Abstract 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 (MELD2) NTCP model with α/β=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/β ratio, (α/β)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/β)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/β is lower than for the tumor in question.

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

Abstract 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.

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 reirradiation (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.

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.

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.

Lung tumor segmentation using electric flow lines for graph cuts

Lung cancer is the most common cause of cancer-related death. A common treatment is radiotherapy where the lung tumors are irradiated with ionizing radiation. The treatment is typically fractionated, i.e. spread out over time, allowing healthy tissue to recover between treatments and allowing tumor cells to be hit in their most sensitive phase. Changes in tumors over the course of treatment allows for an adaptation of the radiotherapy plan based on 3D computer tomography imaging. This paper introduces a method for segmentation of lung tumors on consecutive computed tomography images. These images are normally only used for correction of movements. The method uses graphs based on electric flow lines. The method offers several advantages when trying to replicate manual segmentations. The method gave a dice coefficient of 0.85 and performed better than level set methods and deformable registration.