Impact of mandated drug monitoring on opioid use during highly conformal radiotherapy for oropharynx cancer.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have proliferated due to increasing opioid-related deaths. We evaluated acute opioid use changes for 64 patients treated with highly conformal radiotherapy (RT) following a state-mandated PDMP. METHODS: Patients receiving proton therapy (PT) (n=40), intensity-modulated RT (IMRT) (n=14), or both (n=10) were divided into preintervention (n=26) and postintervention cohorts (n=38); records were reviewed retrospectively under an institutional review board (IRB)-approved tracking protocol. Dosages prescribed during acute therapy (during RT-3 months post-RT) and patient-reported pain (Defense and Veterans Pain Rating Scale) were endpoints. Dosages were treated as responses in Chi-square tests (three-level ordinal response). RESULTS: Overall, 72% (n=46) received opioids; of which 22% (n=10) of all patients and 10% (n=2) of opioid-naive patients continued analgesic management 3 months post-RT. Median total doses were 975 and 1,025 morphine milligram equivalents (MME) in pre- and postintervention groups, with no significant differences in MME prescribed (P=0.8) or uncontrolled pain (P=0.3). Statistically significant factors were tonsil primaries (P<0.01) and alcohol use (P=0.02). Uncontrolled pain episodes during and post-RT did not vary per cohort (P=0.19). CONCLUSIONS: PDMP use was not associated with management changes in patient-reported acute pain during RT (IMRT or PT). Following highly conformal RT, few patients remained on narcotics 3 months post-RT.

CBCT-Based Dose Monitoring and Adaptive Planning Triggers in Head and Neck PBS Proton Therapy.

PURPOSE: To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients. METHODS: For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations. Two different synthetic CT algorithms were tested; the corrected CBCT (corrCBCT) was created using an iterative image correction method and the virtual CT (virtCT) was created by deforming the planning CT to the CBCT, followed by a low-density masking process. Clinical treatment plans were recalculated on the image sets for evaluation. RESULTS: Plan review trigger criteria for adaptive therapy were established after closely reviewing the cohort data. Compared to the vfCT, the corrCBCT and virtCT reliably produced dosimetric data more similar to the gtCT. The average discrepancy in D99 for high-risk clinical target volumes (CTV) was 1.1%, 0.7%, and 0.4% and for standard-risk CTVs was 1.8%, 0.5%, and 0.5% for the vfCT, corrCBCT, and virtCT, respectively. CONCLUSION: Streamlined APT has been achieved with the proposed plan review criteria and CBCT-based synthetic CT workflow.

Local salvage of radiorecurrent prostate cancer.

BACKGROUND: Locally recurrent prostate cancer following primary external beam radiotherapy without distant metastasis is a challenging problem, with no current consensus on the optimal management of these patients. Traditional whole-gland salvage treatments offered up to a 50% 5-year disease-free survival rate but with troubling levels of risk for significant complications. Recent progress in advanced imaging techniques has allowed a more accurate selection of patients with local-only recurrence and a selection of patients that may be suitable for newer partial-gland salvage treatments that may reduce late complications. METHODS: This article reviews advances in patient selection and provides an overview of whole- and partial-gland salvage results from selected recent meta-analyses, multi-institutional series, and studies from centers of excellence for these treatment approaches. RESULTS: Salvage radical prostatectomy produces 5-year relapse-free survival (RFS) rates in the 50%-60% range with severe gastrointestinal (GI) toxicity in < 2% but severe genitourinary (GU) toxicity in 15%-23% of patients. The whole-gland options of high and low dose rate brachytherapy and stereotactic body radiation therapy appear to offer similar 5-year control rates, with low severe GU and GI toxicity rates of 4%-8% and <2%, respectively. Cryotherapy and high-intensity focused ultrasound (HIFU) offer similar 5-year RFS rates but carry significant risks for severe GU and GI toxicity in the range of 10%-27% and <2%, respectively. Early results of partial-gland salvage techniques in selected patients appear promising, with 3-year RFS rates of 48%-72% and rare grade 3 toxicity. CONCLUSION: It is important to understand the relative effectiveness and risks of the various treatment options to effectively counsel patients who face this distressing clinical situation. Whole-gland salvage options offer the possibility of long-term control but with significant risks of severe toxicity. Emerging data for the partial-gland salvage options in appropriately selected patients may offer hope of reasonable control rates with reduced severe toxicity.

Early-stage vocal cord cancer treated with hypofractionated radiotherapy to the larynx with or without concurrent chemotherapy.

BACKGROUND: We report outcomes among patients with T2 and select T3 glottic squamous cell carcinoma (SCC) treated with radiotherapy. METHODS: We reviewed T2 and T3 (only paraglottic space invasion) N0 M0 glottic SCC patients treated with curative-intent hypofractionated larynx radiotherapy, with or without concurrent systemic therapy. RESULTS: Of 71 patients, those who received concurrent chemotherapy (23/71; 32%) had worse prognostic factors, including impaired cord mobility (70% vs. 40%, p = 0.02) and larger median gross tumor volume (3.0 vs. 1.6 cm3 , p = 0.003). Over a median follow-up of 3.8 years, 2-year local control among patients with impaired cord mobility appeared higher for those who received chemotherapy (88% vs. 61%, p = 0.12), but the difference was not statistically significant. Acute and late toxicity rates were not higher among patients who received chemotherapy. CONCLUSIONS: The addition of concurrent platinum-based chemotherapy to hypofractionated larynx radiotherapy among patients with early-stage glottic SCC with impaired cord mobility appears safe and worthy of additional investigation.

Insurance Approval for Definitive Proton Therapy for Prostate Cancer.

PURPOSE: To determine factors that influence insurance approval for definitive proton therapy (PT) for prostate cancer. MATERIALS AND METHODS: Between 2014 and 2018, 1592 insured patients with localized prostate cancer were evaluated and recommended to undergo definitive PT; 547 patients (34.4%) had commercial insurance, whereas 1045 patients (65.6%) had Medicare/Medicaid. Of those with Medicare, 164 patients (15.7%) had Medicare alone; 677 (64.8%) had supplemental plans; and 204 (19.5%) had secondary commercial insurance. Insurance that "covered" PT for prostate cancer implied that it was an indication designated in the coverage policy. "Not covered" means that the insurance policy did not list prostate cancer as an indication for PT. Of all 1592 patients, 1263 (79.3%) belonged to plans that covered PT per policy. However, approval for PT was still required via medical review for 619 patients (38.9%), comparative dosimetry for 56 patients (3.5%), peer-to-peer discussion for 234 patients (14.7%), and administrative law judge hearings for 3 patients (<0.1%). Multivariate analyses of factors affecting approval were conducted, including risk group (low/intermediate versus high), insurance type (commercial versus Medicare/Medicaid), whether PT was included as a covered benefit under the plan (covered versus not covered), and time period (2014-16 versus 2017 versus 2018). RESULTS: On multivariate analysis, factors affecting PT approval for prostate treatment included coverage of PT per policy (97.1% had approval with insurance that covered PT versus 48.6% whose insurance did not cover PT; P < .001); insurance type (32.5% had approval with commercial insurance versus 97.4% with Medicare; P < .001); and time, with 877/987 patients (88.9%) approved between 2014 and 2016, 255/312 patients (81.7%) approved during 2017, and 255/293 patients (87.0%) approved thereafter (P = .02). Clinical factors, including risk group, had no bearing on insurance approval (P = .44). CONCLUSION: Proton insurance approval for prostate cancer has decreased, is most influenced by the type of insurance a patient belongs to, and is unrelated to clinical factors (risk group) in this study. More work is needed to help navigate appropriate access to care and to assist patients seeking definitive PT for prostate cancer treatment.

Heterogeneity in Radiotherapeutic Parameter Assumptions in Cost-Effectiveness Analyses in Prostate Cancer: A Call for Uniformity.

OBJECTIVES: Cost-effectiveness analyses (CEAs) may provide useful data to inform management decisions depending on the robustness of a model's input parameters. We sought to determine the level of heterogeneity in health state utility values, transition probabilities, and cost estimates across published CEAs assessing primarily radiotherapeutic management strategies in prostate cancer. METHODS: We conducted a systematic review of prostate cancer CEAs indexed in MEDLINE between 2000 and 2018 comparing accepted treatment modalities across all cancer stages. Search terms included "cost effectiveness prostate," "prostate cancer cost model," "cost utility prostate," and "Markov AND prostate AND (cancer OR adenocarcinoma)." Included studies were agreed upon. A Markov model was designed using the parameter estimates from the systematic review to evaluate the effect of estimate heterogeneity on strategy cost acceptability. RESULTS: Of 199 abstracts identified, 47 publications were reviewed and 37 were included; 508 model estimates were compared. Estimates varied widely across variables, including gastrointestinal toxicity risk (0%-49.5%), utility of metastatic disease (0.25-0.855), intensity-modulated radiotherapy cost ($21 193-$61 996), and recurrence after external-beam radiotherapy (1.5%-59%). Multiple studies assumed that different radiotherapy modalities delivering the same dose yielded varying cancer control rates. When using base estimates for similar parameters from included studies, the designed model resulted in 3 separate acceptability determinations. CONCLUSIONS: Significant heterogeneity exists across parameter estimates used to perform CEAs evaluating treatment for prostate cancer. Heterogeneity across model inputs yields variable conclusions with respect to the favorability and cost-effectiveness of treatment options. Decision makers are cautioned to review estimates in CEAs to ensure they are up to date and relevant to setting and population.

Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer.

BACKGROUND: To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. MATERIAL AND METHODS: We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. RESULTS: Median follow-up was 8.0 years (0.9-12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. CONCLUSION: Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.

Normal tissue complication probability models for prospectively scored late rectal and urinary morbidity after proton therapy of prostate cancer.

BACKGROUND AND PURPOSE: Photons and protons have fundamentally different properties, i.e. protons have a reduced dose bath but a higher relative biological effectiveness. Photon-based normal tissue complication probability (NTCP) models may therefore not immediately be applicable to proton therapy (PT). The aim was to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively recorded late morbidity data from PT, focusing on rectal morbidity and prostate cancer. MATERIALS AND METHODS: Prospectively collected data were available for 1151 prostate cancer patients treated with passive scattering PT and prescribed target doses of 78-82 Gy (RBE = 1.1) in 2 Gy fractions. Morbidity data (CTCAE v3.0) consisted of two alternative late grade 2 rectal bleeding endpoints: Medical Grade2A (GR2A) and procedural Grade2B (GR2B), as well as late grade 3 + urinary morbidity. GR2A + 2B were observed in 156/1047 patients (15%), GR2B in 45/1047 patients (4%), and urinary grade 3 + in 51/1151 patients (4%). LKB NTCP model parameters (D50, m, and n) were derived by maximum likelihood estimation. RESULTS: For the rectum/rectal wall the volume parameter n was low (0.07-0.14) for both GR2A + 2B and GR2B, as was the m parameter (range: 0.16-0.20). For the bladder/bladder wall both parameters were high (n-range: 0.20-0.36; m-range: 0.32-0.36). D50 parameters were higher for GR2B of the rectum/rectal wall (95.9-98.0 Gy) and bladder/bladder wall (118.1-119.9 Gy), but lower for GR2A2B (71.7-73.6 Gy). CONCLUSION: PT specific LKB NTCP model parameters were derived from a population of more than 1000 patients. The D50 parameter differed for all structures and endpoints and deviated from typical photon-based LKB model values.

Consensus Statement on Proton Therapy for Prostate Cancer.

Proton therapy is a promising but controversial treatment in the management of prostate cancer. Despite its dosimetric advantages when compared with photon radiation therapy, its increased cost to patients and insurers has raised questions regarding its value. Multiple prospective and retrospective studies have been published documenting the efficacy and safety of proton therapy for patients with localized prostate cancer and for patients requiring adjuvant or salvage pelvic radiation after surgery. The Particle Therapy Co-Operative Group (PTCOG) Genitourinary Subcommittee intends to address current proton therapy indications, advantages, disadvantages, and cost effectiveness. We will also discuss the current landscape of clinical trials. This consensus report can be used to guide clinical practice and research directions.

What men want: Results from a national survey on decision making for prostate cancer treatment and research participation.

Data comparing outcomes in prostate cancer and factors affecting treatment choice are sparse. To inform the design of a comparative effectiveness clinical trial, we engaged patients in developing a 28-question survey about decision making on treatment and research participation and dispersed it among men greater than or equal to 50 years of age. The 1046 respondents ranked long-term clinical outcomes as most important in making treatment decisions, specific functional outcomes as slightly less important, and duration, location, and cost of treatment as least important. Treatment choice was strongly impacted by side effect profile. Responses to whether the subject would agree to participation in a randomized trial between two types of radiation with minimal differences in outcomes were "yes" in 15%, "no" in 39%, and "undecided" in 46%. Responses to whether the subject would agree to participation in a randomized trial between two treatment durations with similar outcomes were yes in 36%, no in 24%, and undecided in 40%. Findings suggest many potential patients have strong treatment preferences and are averse to randomization, particularly when outcomes of importance may be affected. Patient engagement in study design and novel nonrandomized trial designs may offer a path to increase clinical trial success.

Long-term Outcomes from Proton Therapy for Sinonasal Cancers.

PURPOSE: To report long-term disease control, survival, and toxicity after proton therapy for sinonasal cancer. PATIENTS AND METHODS: We reviewed 143 cases of adults with nonmetastatic sinonasal cancers treated with primary (18%; n = 26) or adjuvant (82%; n = 117) proton therapy. The most common histologies were squamous cell carcinoma (29%; n = 42), olfactory neuroblastoma (23%; n = 33), and adenoid cystic carcinoma (16%; n = 23). Patients had predominantly advanced-stage disease (T3, 24%, n = 35; T4, 66%, n = 94) and high-grade histology (52%; n = 74). Surgery included endoscopic resection alone (50%) with craniotomy (10%) or open resection (40%), and 31% had gross disease present at radiotherapy. Most (91%) received high-dose (median, 73.6 Gy radiobiological equivalent [GyRBE]; 84% >70 GyRBE) passive-scatter proton therapy using accelerated hyperfractionation (1.2 GyRBE twice daily) and concurrent chemotherapy (70%). Univariate and multivariate models assessed prognostic factors. Grade 3+ toxicities were recorded per Common Terminology Criteria, version 4. Median follow-up was 3.4 years (range, 0.1-12.5 years) overall and 4.9 years (range, 0.9-12.5 years) for living patients. RESULTS: The 5-year outcomes were as follows: local control (LC), 80%; neck control, 96%; local-regional control, 78%; freedom from distant metastases, 71%; and disease-free survival, 62%; cause-specific survival, 64%; and overall survival, 59%. Surgery improved LC, but only with gross total resection (5-year LC 87% versus subtotal resection 62.9%, and biopsy alone 55% (P < 0.001). Gross residual disease was the only significant prognostic factor for local-regional control on multivariate analysis. High-grade, T4, and local recurrence were associated with decreased overall survival. Late (G3+) toxicity occurred in 22% (32 of 143), including central nervous system necrosis and vision loss in 6% (9 of 143) and 3.5% (5 of 143), respectively. CONCLUSION: Proton therapy after gross-total resection provides excellent long-term LC in patients with locally advanced, high-grade sinonasal cancer. Moreover, LC remains strongly associated with long-term survival. With gross disease, about 60% of patients had long-term LC with proton therapy and induction or concurrent chemotherapy.

Passively Scattered Proton Therapy for Nonmelanoma Skin Cancer with Clinical Perineural Invasion.

PURPOSE: To report our experience with the delivery of passively scattered proton therapy in the management of nonmelanoma skin cancers with clinical perineural invasion. MATERIALS AND METHODS: We reviewed the medical records of patients who received definitive or postoperative proton therapy for nonmelanoma skin cancer with clinical perineural invasion at our institution and updated patient follow-up when possible. All patients were treated with curative intent with or without the delivery of concurrent systemic therapy. We report disease control rates and the rates of late toxicity among this cohort. RESULTS: Twenty-six patients treated between 2008 and 2017 were included in the analysis. Following proton therapy, the 3-year overall, cause-specific, and disease-free survival rates were 59%, 73%, and 60%, respectively. The 3-year local control, local regional control, and distant metastasis-free survival rates were 80%, 65%, and 96%, respectively. On univariate analysis, surgical resection before radiation therapy significantly improved local regional control rates at 3 years (55% versus 86%; P = .04). Grade 3+ late toxicities occurred in 13 patients (50%) and the most common toxicities included grade 3+ keratitis of the ipsilateral eye, which occurred in 4 patients (15%) and grade 3+ brain necrosis in 4 patients (15%). CONCLUSION: Proton therapy is effective in the management of nonmelanoma skin cancer with clinical perineural invasion. Although disease control and complication rates compare favorably to those previously published for photon-based radiation therapy, the risk for late toxicity is significant and patients should be appropriately counseled.

Postoperative or Salvage Proton Radiotherapy for Prostate Cancer After Radical Prostatectomy.

PURPOSE: Postprostatectomy radiation improves disease control, but limited data exist regarding outcomes, toxicities, and patient-reported quality of life with proton therapy. METHOD AND MATERIALS: The first 102 patients who were enrolled on an outcome tracking protocol between 2006 and 2017 and treated with double-scattered proton therapy after prostatectomy were retrospectively reviewed. Eleven (11%) received adjuvant radiation, while 91 (89%) received salvage radiation. Seventy-four received double-scattered proton therapy to the prostate bed only. Twenty-eight received a double-scattered proton therapy prostate-bed boost after prostate-bed and pelvic-node treatment. Eleven adjuvant patients received a median dose of 66.6 GyRBE (range, 66.0-70.2). Ninety-one salvage patients received a median dose of 70.2 GyRBE (range, 66.0-78.0). Forty-five patients received androgen deprivation therapy for a median 9 months (range, 1-30). Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0 criteria, and patient-reported quality-of-life data were reviewed. RESULTS: The median follow-up was 5.5 years (range, 0.8-11.4 years). Five-year biochemical relapse-free and distant metastases-free survival rates were 72% and 91% for adjuvant patients, 57% and 97% for salvage patients, and 57% and 97% overall. Acute and late grade 3 or higher genitourinary toxicity rates were 1% and 7%. No patients had grade 3 or higher gastrointestinal toxicity. Acute and late grade 2 gastrointestinal toxicities were 5% and 2%. The mean values and SDs of the International Prostate Symptom Score, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 7.5 (SD = 5.9), 10.2 (SD = 8.3), 92.8 (SD = 11.1), and 91.2 (SD = 6.4), respectively, at baseline, and 12.1 (SD = 9.1), 10.1 (SD = 6.7), 87.3 (SD = 18), and 86.7 (SD = 13.8) at the 5-year follow-up. CONCLUSION: High-dose postprostatectomy proton therapy provides effective long-term biochemical control and freedom from metastasis, with low acute and long-term gastrointestinal and genitourinary toxicity.

Current Role of Radiotherapy in the Management of Oral Cavity Squamous Cell Carcinoma.

STUDY DESIGN: Literature review. OBJECTIVE: To review the current role of radiotherapy (RT) in the management of oral cavity squamous cell carcinoma (SCC). METHODS: Review of selected literature. RESULTS: T1-T2N0 SCCs may be treated with either RT alone or surgery with a high likelihood of cure. The pendulum swung toward surgery with postoperative RT (PORT) added depending on the pathological findings in the mid 1980s. Patients with positive margins, extranodal extension (ENE), and/or 4 or more positive nodes receive concomitant chemotherapy (POCRT). Patients with T3-T4 and/or positive regional nodes are treated with surgery and PORT alone or POCRT. The likelihood of cure is moderate to low depending on extent of disease. The likelihood of major complications ranges from 10% to 30% depending on the method of reconstruction and the aggressiveness of postoperative PORT/POCRT. Patients with very advanced disease are treated with palliative RT, chemotherapy, or supportive care. CONCLUSIONS: The role of RT in the management of oral cavity SCC is primarily in the postoperative setting with palliative RT being reserved for those with very advanced disease where the likelihood of cure is remote.

A comparative study of prostate PTV margins for patients using hydrogel spacer or rectal balloon in proton therapy.

PURPOSE: To compare the planning target volume (PTV) margins needed for prostate patients who have used hydrogel spacer or rectal balloon during proton treatments. METHOD: Total of 190 prostate patients treated with proton therapy during 2017 were selected for this study. Of these patients, 96 had hydrogel spacer injection and 94 patients had only rectal balloons insertion. All patients had implanted gold markers inside the prostate for daily target alignment. Post-treatment radigraphs were obtained to evaluate prostate intrafraction motion. The systematic and random components of patient setup residual error and prostate intrafraction motion error were obtained. PTV margins were calculated using the van Herk formula for both patient groups. RESULTS: For setup residual error, the mean values in the superior-inferior (SI) direction and the variances in the left-right (LR) direction were statistically different between the two groups. For intrafraction motion, there were significant differences of the mean values in the SI direction and of the variances in both LR and anterior-posterior (AP) directions. The population PTV margins for hydrogel spacer group were 2.6 mm, 3.3 mm, and 1.6 mm in LR, SI, AP directions, respectively. For the rectal balloon group, the PTV margins were 2.1 mm, 3.1 mm, and 2.0 mm in LR, SI, AP directions, respectively. CONCLUSION: Statistically significant differences were observed in the patient setup and prostate intrafraction motion errors of the two patient groups. However, under the current protocol of bladder preparation and daily marker-based x-ray image-guidance, population PTV margins were comparable between the two patient groups.

Multivariate normal tissue complication probability models for rectal and bladder morbidity in prostate cancer patients treated with proton therapy.

BACKGROUND AND PURPOSE: Normal tissue complication probability (NTCP) models applied for model-based patient selection to proton therapy (PT) have usually been derived using dose/volume histogram (DVH) parameters from photon-based radiotherapy. This study aimed to derive PT-specific multivariate NTCP models that also accounted for the spatial dose distribution (rectum only) as well as non-dose/volume related factors. MATERIALS AND METHODS: The study included rectum and bladder DVHs, 2D rectal dose maps and relevant patient/treatment characteristics from 1151 prostate cancer cases treated with PT. Prospectively scored Grade 2 late rectal bleeding (CTCAE v3.0, also procedural interventions separately) (n = 156 (15%)) and Grade 3+ GU morbidity (n = 51 (4%)) were entered into a multivariate logistic regression analysis. Model evaluation included assessment of the area under the receiver operating characteristic curve (AUC). RESULTS: Anticoagulant use was a dominant predictor, chosen in four of the six rectum models and in the bladder model. Age was a dominant predictor in all procedural only rectum models while prostate volume, bladder D5% and V75Gy were predictors in the bladder model. The selection frequency of the dose/volume predictors varied widely, where the percentage of the anterior rectum surface receiving >=75 Gy was the most robust. AUC values ranged from 0.58 to 0.70 across all models, with no clear difference between the DVH- and spatial-based models for the rectum. CONCLUSION: Anticoagulant use and age were the most prominent predictors in the NTCP models. V75Gy of the rectal wall and the bladder was a predictor in the DVH-based models of the rectum and bladder respectively.

Cross-modality applicability of rectal normal tissue complication probability models from photon- to proton-based radiotherapy.

BACKGROUND AND PURPOSE: Proton therapy (PT) is currently being studied to improve normal tissue (NT) sparing beyond what can be achieved with conventional photon-based therapy. Compared to photons, PT dose distributions have a reduced NT low-to-intermediate 'dose bath' and a different biological effectiveness, questioning the applicability of photon-based NT complication probability (NTCP) models to PT. The aim of this study was to assess the applicability of photon-based NTCP models to rectum morbidity outcomes following PT. MATERIALS AND METHODS: Treatment planning and morbidity data from 1151 prostate cancer patients treated with passive scattering PT and from 159 patients treated with conventional 3D conformal four-field photon therapy were analysed. Prospectively scored gastrointestinal morbidities (grade >=2) were analysed, with a total of 184 events (protons; medical and procedural) and 12 events (photons; procedural only), respectively. Rectal dose volume histograms were extracted for all patients in both cohorts and used as input to two different NTCP models, with up to six different published photon-based parameter sets. RESULTS: Photon-based rectal NTCP models either over- or underestimated the clinically observed gastrointestinal morbidity when used on the proton cohort, depending on the choice of endpoint (p < 0.05 for all parameter sets, for both morbidity classifications). Four of the six photon-based NTCP models showed a good fit to the photon outcome data (p > 0.05). CONCLUSION: There were large differences in morbidity predictions between cohorts and modalities, indicating that the validity of NTCP models and parameters across institutions and treatment modalities should be carefully investigated prior to clinical application.