B. Yaremko

Systematic review of dose―volume parameters in the prediction of esophagitis in thoracic radiotherapy

PURPOSEnWith dose escalation and increasing use of concurrent chemoradiotherapy, radiation esophagitis (RE) remains a common treatment-limiting acute side effect in the treatment of thoracic malignancies. The advent of 3DCT planning has enabled investigators to study esophageal dose-volume histogram (DVH) parameters as predictors of RE. The purpose of this study was to assess published dosimetric parameters and toxicity data systematically in order to define reproducible predictors of RE, both for potential clinical use, and to provide recommendations for future research in the field.nnnMATERIALS AND METHODSnWe performed a systematic literature review of published studies addressing RE in the treatment of lung cancer and thymoma. Our search strategy included a variety of electronic medical databases, textbooks and bibliographies. Both prospective and retrospective clinical studies were included. Information relating to the relationship among measured dosimetric parameters, patient demographics, tumor characteristics, chemotherapy and RE was extracted and analyzed.nnnRESULTSnEighteen published studies were suitable for analysis. Eleven of these assessed acute RE, while the remainder assessed both acute and chronic RE together. Heterogeneity of esophageal contouring practices, individual differences in information reporting and variability of RE outcome definitions were assessed. Well-described clinical and logistic modeling directly related V(35Gy), V(60Gy) and SA(55Gy) to clinically significant RE.nnnCONCLUSIONSnSeveral reproducible dosimetric parameters exist in the literature, and these may be potentially relevant in the prediction of RE in the radiotherapy of thoracic malignancies. Further clarification of the predictive relationship between such standardized dosimetric parameters and observed RE outcomes is essential to develop efficient radiation treatment planning in locally advanced NSCLC in the modern concurrent chemotherapy and image-guided IMRT era.

Intensity modulated radiotherapy of non-small-cell lung cancer incorporating SPECT ventilation imaging.

PURPOSEnThe authors performed this retrospective study to investigate the impact of using ventilation scans obtained from single photon emission computed tomography (SPECT) in selecting beam directions in intensity modulated radiation therapy (IMRT) planning in lung cancer radiotherapy to spare dosimetrically well ventilated lung.nnnMETHODSnFor ten consecutive stage III non-small-cell lung cancer patients, the authors obtained both ventilation/perfusion SPECT scans and four-dimensional CT scans for treatment planning purposes. Each ventilation scan was registered with the corresponding planning CT and ventilation volumes corresponding to either > or = 50% (vv50) or > or = 70% (vv70) of the maximum SPECT count were automatically segmented. For each patient, three IMRT plans were generated: One using nine equally spaced beams optimized according to nonfunctional lung based mean lung dose and lung v20; a second using nine equally spaced beams optimized to avoid vv50 and vv70; and a third plan using only three beams with gantry angles chosen based on minimum mean ventilated lung dose calculated for each conformal beam at every 10 degrees gantry angle avoiding vv50 and vv70. Resultant dose volume histogram indices were calculated for each plan and were compared with respect to calculated SPECT-based ventilation parameters in order to quantify the potential utility of ventilation SPECT in this setting.nnnRESULTSnTwo patient groups were identified based on (i) the overlap volume between PTV and vv50 and (ii) the average angular mean ventilated lung dose (AAMvLD). The first parameter quantifies the proximity of the PTV to well ventilated lung and the second parameter quantifies the degree of ventilation that surrounds the PTV. For group 1 patients, < or = 5% of the vv50 overlapped with the PTV. For group 2 patients, > 5% of the vv50 overlapped the PTV. Group 1 was further classified into subgroups 1A and 1B: For subgroup 1A, AAMvLD is >18 Gy, implying that the functional lung surrounds the PTV; for subgroup 1B, AAMvLD is <18 Gy, implying that the well ventilated lung does not completely surround PTV. For subgroup 1A, the plans generated using ventilated lung avoidance reduced dose to vv50 and vv70, with below tolerance dose to normal lung and acceptable coverage of the PTV. For subgroup 1B, the dose to the total lung and well ventilated lung are reduced with the beam direction optimization for the three-beam plan. For group 2, there was no significant dosimetric advantage of using SPECT-based ventilation information in IMRT plan optimization.nnnCONCLUSIONSnIn conclusion, it is feasible to use SPECT ventilation scans to optimize IMRT beam direction and, subsequently, to reduce dose to ventilated lung when overlap of the PTV and the ventilated lung is minimal and that the PTV is not surrounded by the ventilated lung. The potential benefit of ventilation SPECT scanning can be determined by preplanning assessment of overlap volumes and the AAMvLD.

Phase I Trial of Simultaneous In-Field Boost With Helical Tomotherapy for Patients With One to Three Brain Metastases

PURPOSEnStereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present studys objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT.nnnMETHODS AND MATERIALSnThe inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort.nnnRESULTSnA total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients.nnnCONCLUSIONnThe delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.

Assessment of function and quality of life in a phase II multi-institutional clinical trial of fractionated simultaneous in-field boost radiotherapy for patients with 1–3 metastases

Abstract We examined functional outcomesxa0and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1–3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30xa0Gy/10)xa0+xa0simultaneous FSRT, (60xa0Gy/10). Median overall follow-up and survival was 5.4xa0months, 6xa0month actuarial intra-lesional control was 78xa0%; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min–Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70–100), 28 (21–30) and 143 (98–153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall toxa0<27) ranged from 26 to 38xa0% for KPS, 32–59xa0% for FACT-Br and 0–16xa0% for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (≤6xa0months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6xa0weeks to 3xa0months) with no significant change in MMSE. The effects on function and quality of life of this integrated treatment of WBRTxa0+xa0simultaneous FSRT were similar to other published series combining WBRTxa0+xa0radiosurgery.

A phase II trial to evaluate single-dose stereotactic body radiation therapy (SBRT) prior to surgery for early-stage breast carcinoma: SIGNAL (stereotactic image-guided neoadjuvant ablative radiation then lumpectomy) trial

AbstractBackgroundBreast-conserving therapy has become a preferred option in the treatment of early breast cancer. Current breast-conserving therapy includes 3–5xa0weeks of external beam radiotherapy to the whole breast, sometimes followed by a 1–2-week boost to the tumor bed. However, the duration of the radiation regimen can be prohibitive for the elderly, infirm or immobile patients, those patients who live far from the cancer center, or those who have difficulty taking an extended leave of absence. We propose to treat these patients with a single dose of radiation preoperatively, thereby shortening the total treatment time.MethodsThis is a single-arm phase II case series trial, conducted on 120 patients with early breast cancer who will be accrued from multidisciplinary breast cancer clinics. These patients will have research biopsies taken at the time of enrollment and will undergo radiation planning with CT simulation and PET/MRI. A single dose of 21xa0Gy will then be delivered in the prone position to the tumor. A second research biopsy will be taken, then lumpectomy will be performed. This entire procedure will be completed within 1xa0week (7xa0days). The primary endpoint is rate of toxicity (≥grade 2 fibrosis), and secondary endpoints include cosmetic results, quality of life, and rate of recurrence.DiscussionThis study will assess the toxicity associated with using a single preoperative dose of radiation as a replacement for standard adjuvant radiotherapy in breast-conserving therapy. Results of this trial will guide the design of a possible phase III study.n Trial registration: Clinicaltrials.gov identifier: NCT02212860

Sci—Fri AM: Imaging — 04: SPECT‐based functional lung imaging in the prediction of radiation pneumonitis: A retrospective clinical and dosimetric correlation

PURPOSEnTo investigate whether functionally-weighted dose-volume histogram (DVH) parameters are more predictive of radiation-induced pneumonitis (RP) than standard parameters such as V20 and mean lung dose (MLD).nnnMATERIALS AND METHODSnA retrospective chart review identified 26 patients who received curative-intent radiation therapy for primary carcinoma of the lung. Prior to treatment, all patients received single photon emission computed tomography (SPECT) to assess both lung ventilation and lung perfusion. Patients were assessed for clinical RP using standard criteria and were separated into a non-RP group (RP grade < 2) and an RP-group (RP grade ≥ 2). Standard DVH parameters (V10, V20, V30, MLD) and their function-weighted counterparts (for perfusion: pF10, pF20, pF30, pMLD; for ventilation: vF10, vF20, vF30, vMLD) were evaluated for each group. Receiver operating characteristics (ROC) curves were created and the area under the curve (AUC) computed.nnnRESULTSn7 of 26 patients had grade ≥ 2 pneumonitis. Both pF20 (p=0.022) and vF20 (p=0.036) were significantly different between the 2 groups; V20 was not (p=0.06). Both pF30 (p=0.008) and vF30 (p=0.025) were significantly different between groups while V30 failed to reach significance (p=0.072). Standard MLD (p=0.011), pMLD (p=0.001), and vMLD (p=0.011) were all significantly different. The ROC curves indicated that both the perfusion-weighted parameters and the ventilation-weighted parameters outperformed the standard DVH parameters as predictors of RP grade ≥2.nnnCONCLUSIONSnSPECT-based, function-weighted DVH parameters appear to be useful as predictors of RP.

Poster — Thurs Eve‐40: The potential of using SPECT ventilation information with IMRT for functional lung avoidance in radiotherapy of non small cell lung cancer

We have investigated the feasibility of using ventilation scans obtained from single photon emission computed tomography (SPECT) in intensity-modulated radiation therapy (IMRT) planning in lung cancer radiotherapy to avoid well functioning lung. We fused SPECT ventilation scans acquired at GE Hawkeye SPECT-CT of ten stage-III lung radiotherapy patients with planning CT in treatment planning system (Pinnacle v8.0, Philips Medical Systems). We automatically segment out 50% and 70% ventilated volumes. For each patient, we generated IMRT plans using nine equally spaced beams with and without avoiding well ventilated volume. They were compared with three beam IMRT plans with beam directions chosen to minimize the mean dose to the ventilated lung volumes, while keeping cord dose below tolerance and dose uniformity in the target. The plans generated using functional lung avoidance information reduces the doses to the functioning lung. With both IMRT avoidance plans, we could not obtain better functional avoidance or lower V-20Gy (volume receiving 20Gy or more) for total lung when the planning target volume (PTV) was surrounded by functional lung volumes. We were able to achieve better ventilated lung avoidance and lower total lung V-20Gy when the PTV is close to, but not surrounded by functioning lung volumes. For patients with the PTV that is far from 50% and 70% functional lung volumes, three-field IMRT spare the ventilated lung as well as nine-field IMRT ventilation avoidance plan, with a lower total lung V20-Gy.