Organ sparing treatment for penile cancer using a 3D-printed high-dose-rate brachytherapy applicator.

PURPOSE: We present a case study of the treatment of localized squamous cell carcinoma on the glans penis with a custom-fabricated high-dose-rate (HDR) brachytherapy applicator. METHODS AND MATERIALS: A cylindrically shaped applicator was fabricated with eight embedded channels suitable for standard plastic brachytherapy catheters. An additional custom silicone bolus/sleeve was designed to be used with the 3D-printed applicator to provide an additional offset from the source to skin to reduce the surface dose and for patient comfort. RESULTS: The patient (recurrent cT1a penile cancer) underwent CT simulation, and the brachytherapy plan was created with a nominal prescription dose of 40 Gy in 10 fractions given bidaily to the surface, and 35 Gy at 5 mm depth. Dose coverage to the clinical target volume was 94% (D90). Most fractions were treated with only 5-10 min of setup time. Follow up visits up to 1 year showed no evidence of disease with no significant changes in urinary and sexual function and limited cosmetic detriment to the patient. CONCLUSIONS: Patient-specific organ-sparing HDR plesiotherapy using 3D printing technology can provide reliable and reproducible patient setup and may be effective in achieving disease control for superficial penile cancer, although preserving patient quality of life.

Thermal ablation compared to stereotactic body radiation therapy for hepatocellular carcinoma: A multicenter retrospective comparative study.

BACKGROUND AIMS: Early-stage HCC can be treated with thermal ablation or stereotactic body radiation therapy (SBRT). We retrospectively compared local progression, mortality, and toxicity among patients with HCC treated with ablation or SBRT in a multicenter, US cohort. APPROACH RESULTS: We included adult patients with treatment-naïve HCC lesions without vascular invasion treated with thermal ablation or SBRT per individual physician or institutional preference from January 2012 to December 2018. Outcomes included local progression after a 3-month landmark period assessed at the lesion level and overall survival at the patient level. Inverse probability of treatment weighting was used to account for imbalances in treatment groups. The Cox proportional hazard modeling was used to compare progression and overall survival, and logistic regression was used for toxicity. There were 642 patients with 786 lesions (median size: 2.1 cm) treated with ablation or SBRT. In adjusted analyses, SBRT was associated with a reduced risk of local progression compared to ablation (aHR 0.30, 95% CI: 0.15-0.60). However, SBRT-treated patients had an increased risk of liver dysfunction at 3 months (absolute difference 5.5%, aOR 2.31, 95% CI: 1.13-4.73) and death (aHR 2.04, 95% CI: 1.44-2.88, p < 0.0001). CONCLUSIONS: In this multicenter study of patients with HCC, SBRT was associated with a lower risk of local progression compared to thermal ablation but higher all-cause mortality. Survival differences may be attributable to residual confounding, patient selection, or downstream treatments. These retrospective real-world data help guide treatment decisions while demonstrating the need for a prospective clinical trial.

Quality Metric to Assess Adequacy of Hydrogel Rectal Spacer Placement for Prostate Radiation Therapy and Association of Metric Score With Rectal Toxicity Outcomes.

Purpose: Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT). Methods and Materials: A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated. Results: The majority of the analyzed cohort had an SQS of 1 (n = 17; 41%) or 2 (n = 18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P = .002), maximum dose to 1 cc of rectum (D1cc; P = .004), and volume of rectum receiving ≥100% of prescription dose (V45; P = .046) and ≥40 Gy (V40; P = .005). SQS was also associated with a higher incidence of (P = .01) and highest-graded late rectal toxicity (P = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity. Conclusions: We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT.

Ablative Radiation Therapy in Oligometastatic Pancreatic Cancer to Delay Polyprogression, Limit Chemotherapy, and Improve Outcomes.

PURPOSE: The oligometastatic state is observed in patients across many malignancies, with increased recognition regarding improved outcomes after local therapies. However, there is limited data specifically regarding pancreatic ductal adenocarcinoma. We hypothesized that an oligometastatic pancreatic ductal adenocarcinoma (OPanc) phenotype would benefit from stereotactic ablative radiation therapy (SABR) to all active metastatic sites. Here, we report our institutional experience of SABR-treated OPanc to evaluate the feasibility of the approach. METHODS AND MATERIALS: A retrospective review of patients with synchronous or metachronous OPanc (1 to 5 metastases) who received SABR to all active metastatic sites was performed. We identified a comparable group of patients with similar metastatic burden, range of CA19-9 levels, and no progression for at least 5 months who did not receive SABR. We compared overall survival as the primary outcome, and polyprogression-free survival and time off chemotherapy as the secondary exploratory assessments. A third group presenting with stage IV pancreatic ductal adenocarcinoma and more than 5 distant lesions (polymetastatic) was identified to help define expected outcomes after polyprogression. RESULTS: Our study included 20 patients with OPanc receiving SABR and 21 who did not. SABR was delivered to 38 metastatic tumors. Out of the 20 SABR-treated OPanc patients, 17 (85%) had 6 or more months of time off chemotherapy, compared with 7 patients (33.3%) among the chemotherapy-treated group. Median polyprogression-free survival was 40 and 14 months (hazard ratio = 0.2; 95% confidence interval, 0.07-0.54; P = .0009), and overall survival was 42 and 18 months (hazard ratio = 0.21; 95% confidence interval, 0.08-0.53; P = .0003), for SABR- and chemotherapy-treated cohorts, respectively. CONCLUSIONS: Management of OPanc with SABR as local regional therapy could improve outcomes in a selected population and warrants prospective evaluation.

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer.

Purpose: Stereotactic ablative radiation (SAbR) has been increasingly used in prostate cancer (PCa) given its convenience and cost efficacy. Optimal doses remain poorly defined with limited prospective comparative trials and long-term safety/efficacy data at higher dose levels. We analyzed toxicity and outcomes for SAbR in men with localized PCa at escalated 45 Gy in 5 fractions. Methods and Materials: This study retrospectively analyzed men from 2015 to 2019 with PCa who received linear-accelerator-based SAbR to 45 Gy in 5 fractions, along with perirectal hydrogel spacer, fiducial placement, and MRI-based planning. Disease control outcomes were calculated from end of treatment. Minimally important difference (MID) assessing patient-reported quality of life was defined as greater than a one-half standard deviation increase in American Urological Association (AUA) symptom score after SAbR. Results: Two-hundred and forty-nine (249) low-, intermediate-, and high-risk PCa patients with median follow-up of 14.9 months for clinical toxicity were included. Acute urinary grade II toxicity occurred in 20.4% of patients. Acute grade II GI toxicity occurred in 7.3% of patients. For follow-up > 2 years (n = 69), late GU and GI grade ≥III toxicity occurred in 5.8% and 1.5% of patients, respectively. MID was evident in 31.8%, 23.4%, 35.8%, 37.0%, 33.3%, and 26.7% of patients at 3, 6, 12, 24, 36, and 48 months, respectively. The median follow-up for biochemical recurrence was 22.6 months with biochemical failure-free survival of 100% at 1 year (n = 226) and 98.7% for years 2 (n = 113) and 3 (n = 54). Conclusions: SAbR for PCa at 45 Gy in 5 fractions shows an encouraging safety profile. Prospective studies with longer follow-up are warranted to establish this dose regimen as standard of care for PCa.

Brachial Plexus Tolerance to Single-Session SABR in a Pig Model.

PURPOSE: The single-session dose tolerance of the spinal nerves has been observed to be similar to that of the spinal cord in pigs, counter to the perception that peripheral nerves are more tolerant to radiation. This pilot study aims to obtain a first impression of the single-session dose-response of the brachial plexus using pigs as a model. METHODS AND MATERIALS: Ten Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiotherapy. A 2.5-cm length of the left-sided brachial plexus cords was irradiated. Pigs were distributed in 3 groups with prescription doses of 16 (n = 3), 19 (n = 4), and 22 Gy (n = 3). Neurologic status was assessed by observation for changes in gait and electrodiagnostic examination. Histopathologic examination was performed with light microscopy of paraffin-embedded sections stained with Luxol fast blue/periodic acid-Schiff and Masson's trichrome. RESULTS: Seven of the 10 pigs developed motor deficit to the front limb of the irradiated side, with a latency from 5 to 8 weeks after irradiation. Probit analysis of the maximum nerve dose yields an estimated ED50 of 19.3 Gy for neurologic deficit, but the number of animals was insufficient to estimate 95% confidence intervals. No motor deficits were observed at a maximum dose of 17.6 Gy for any pig. Nerve conduction studies showed an absence of sensory response in all responders and absent or low motor response in most of the responders (71%). All symptomatic pigs showed histologic lesions to the left-sided plexus consistent with radiation-induced neuropathy. CONCLUSIONS: The single-session ED50 for symptomatic plexopathy in Yucatan minipigs after irradiation of a 2.5-cm length of the brachial plexus cords was determined to be 19.3 Gy. The dose-response curve overlaps that of the spinal nerves and the spinal cord in the same animal model. The relationship between the brachial plexus tolerance in pigs and humans is unknown, and caution is warranted when extrapolating for clinical use.

SABR for High-Risk Prostate Cancer: A Prospective Multilevel MRI-Based Dose Escalation Trial.

PURPOSE: Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)-based 5-fraction SABR in patients with HR-PCa. METHODS AND MATERIALS: This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate <33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events. RESULTS: Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively. CONCLUSIONS: SABR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.

Exploratory ensemble interpretable model for predicting local failure in head and neck cancer: the additive benefit of CT and intra-treatment cone-beam computed tomography features.

BACKGROUND: Local failure (LF) following chemoradiation (CRT) for head and neck cancer is associated with poor overall survival. If machine learning techniques could stratify patients at risk of treatment failure based on baseline and intra-treatment imaging, such a model could facilitate response-adapted approaches to escalate, de-escalate, or switch therapy. METHODS: A 1:2 retrospective case control cohort of patients treated at a single institution with definitive radiotherapy for head and neck cancer who failed locally, in-field at a primary or nodal structure were included. Radiomic features were extracted from baseline CT and CBCT scans at fractions 1 and 21 (delta) of radiotherapy with PyRadiomics and were selected for by: reproducibility (intra-class correlation coefficients ≥0.95), redundancy [maximum relevance and minimum redundancy (mRMR)], and informativeness [recursive feature elimination (RFE)]. Separate models predicting LF of primaries or nodes were created using the explainable boosting machine (EBM) classifier with 5-fold cross-validation for (I) clinical only, (II) radiomic only (CT1 and delta features), and (III) fused models (clinical + radiomic). Twenty-five iterations were performed, and predicted scores were averaged with a parallel ensemble design. Receiver operating characteristic curves were compared between models with paired-samples t-tests. RESULTS: The fused ensemble model for primaries (using clinical, CT1, and delta features) achieved an AUC of 0.871 with a sensitivity of 78.3% and specificity of 90.9% at the maximum Youden J statistic. The fused ensemble model trended towards improvement when compared to the clinical only ensemble model (AUC =0.788, P=0.134) but reached significance when compared to the radiomic ensemble model (AUC =0.770, P=0.017). The fused ensemble model for nodes achieved an AUC of 0.910 with a sensitivity of 100.0% and specificity of 68.0%, which also trended towards improvement when compared to the clinical model (AUC =0.865, P=0.080). CONCLUSIONS: The fused ensemble EBM model achieved high discriminatory ability at predicting LF for head and neck cancer in independent primary and nodal structures. Although an additive benefit of delta radiomics over clinical factors could not be proven, the results trended towards improvement with the fused ensemble model, which are promising and worthy of prospective investigation in a larger cohort.

Automatic liver tumor localization using deep learning-based liver boundary motion estimation and biomechanical modeling (DL-Bio).

PURPOSE: Recently, two-dimensional-to-three-dimensional (2D-3D) deformable registration has been applied to deform liver tumor contours from prior reference images onto estimated cone-beam computed tomography (CBCT) target images to automate on-board tumor localizations. Biomechanical modeling has also been introduced to fine-tune the intra-liver deformation-vector-fields (DVFs) solved by 2D-3D deformable registration, especially at low-contrast regions, using tissue elasticity information and liver boundary DVFs. However, the caudal liver boundary shows low contrast from surrounding tissues in the cone-beam projections, which degrades the accuracy of the intensity-based 2D-3D deformable registration there and results in less accurate boundary conditions for biomechanical modeling. We developed a deep-learning (DL)-based method to optimize the liver boundary DVFs after 2D-3D deformable registration to further improve the accuracy of subsequent biomechanical modeling and liver tumor localization. METHODS: The DL-based network was built based on the U-Net architecture. The network was trained in a supervised fashion to learn motion correlation between cranial and caudal liver boundaries to optimize the liver boundary DVFs. Inputs of the network had three channels, and each channel featured the 3D DVFs estimated by the 2D-3D deformable registration along one Cartesian direction (x, y, z). To incorporate patient-specific liver boundary information into the DVFs, the DVFs were masked by a liver boundary ring structure generated from the liver contour of the prior reference image. The network outputs were the optimized DVFs along the liver boundary with higher accuracy. From these optimized DVFs, boundary conditions were extracted for biomechanical modeling to further optimize the solution of intra-liver tumor motion. We evaluated the method using 34 liver cancer patient cases, with 24 for training and 10 for testing. We evaluated and compared the performance of three methods: 2D-3D deformable registration, 2D-3D-Bio (2D-3D deformable registration with biomechanical modeling), and DL-Bio (DL model prediction with biomechanical modeling). The tumor localization errors were quantified through calculating the center-of-mass-errors (COMEs), DICE coefficients, and Hausdorff distance between deformed liver tumor contours and manually segmented "gold-standard" contours. RESULTS: The predicted DVFs by the DL model showed improved accuracy at the liver boundary, which translated into more accurate liver tumor localizations through biomechanical modeling. On a total of 90 evaluated images and tumor contours, the average (± sd) liver tumor COMEs of the 2D-3D, 2D-3D-Bio, and DL-Bio techniques were 4.7 ± 1.9 mm, 2.9 ± 1.0 mm, and 1.7 ± 0.4 mm. The corresponding average (± sd) DICE coefficients were 0.60 ± 0.12, 0.71 ± 0.07, and 0.78 ± 0.03; and the average (± sd) Hausdorff distances were 7.0 ± 2.6 mm, 5.4 ± 1.5 mm, and 4.5 ± 1.3 mm, respectively. CONCLUSION: DL-Bio solves a general correlation model to improve the accuracy of the DVFs at the liver boundary. With improved boundary conditions, the accuracy of biomechanical modeling can be further increased for accurate intra-liver low-contrast tumor localization.

A systematic review of intraluminal high dose rate brachytherapy in the management of malignant biliary tract obstruction and cholangiocarcinoma.

PURPOSE: To conduct a systematic review evaluating the impact of high dose rate (HDR) intraluminal brachytherapy (ILBT) in the management of malignant biliary obstruction and cholangiocarcinoma with specific focus on stent patency, clinical outcomes and toxicities. METHODS AND MATERIALS: A review of published articles was conducted using Medline, Embase and Cochrane databases using the search terms "bile duct carcinoma" or "cholangiocarcinoma" or "bile duct neoplasms" in combination with "brachytherapy" or "high dose rate brachytherapy" or "HDR brachytherapy". Studies published in English and reporting outcomes of ≥10 patients were included in the review. Only the most recent experience was included if same patients were included in sequential publications. RESULTS: Seventeen studies were identified that met the inclusion criteria. Significant heterogeneity was observed in treatment regimens, which included use of surgery, external beam radiation (EBRT), and/or intra-arterial and intravenous chemotherapy in conjunction with ILBT. Nevertheless, among the included studies, use of ILBT appeared to result in longer duration of stent patency: 10 months with ILBT compared to 4-6 months without ILBT. A trend was observed towards prolonged local control and improved complete and partial response rates in patients treated with ILBT with or without EBRT. Weighted mean overall survival of patients treated with ILBT alone was 11.8 months compared to 10.5 months for those that received EBRT +/- chemotherapy in addition to ILBT. The included studies reported low complication rates and toxicity related to ILBT. CONCLUSION: Brachytherapy can be an effective and safe tool in the management of malignant biliary tract obstruction in combination with stenting. Both retrospective and prospective studies have suggested improved outcomes when HDR ILBT is combined with percutaneous stenting.

Hydrogel Spacer Rectal Wall Infiltration Associated With Severe Rectal Injury and Related Complications After Dose Intensified Prostate Cancer Stereotactic Ablative Radiation Therapy.

The risk of rectal toxicity during and after prostate cancer radiation therapy is common to all treatment regimens. Hydrogel rectal spacers are increasingly being used to mitigate this risk and to facilitate dose-escalation, but also may infiltrate the rectal wall, with unclear clinical implication. We present a case of significant infiltration associated with severe late rectal injury (grade 4) and further grade 3 to 4 sequelae (recto-urethral fistula and associated osteomyelitis requiring exenteration) after high-dose stereotactic body radiation therapy for localized prostate cancer. The injury's temporal pattern associated with the expected timing of gel dissolution and displacement of infiltrated rectal layers potentially toward high dose regions together suggest a contributing role of the infiltration to the injury. In light of the rapid increase of hydrogel rectal spacer utilization, we review the case's evolution, concerning imaging findings, and associated literature and make suggestions regarding treatment planning and endoscopic assessment in the setting of infiltration or expected injury.

A Multi-Institutional Phase 2 Trial of High-Dose SAbR for Prostate Cancer Using Rectal Spacer.

PURPOSE: High-dose SABR for prostate cancer offers the radiobiologic potency of the most intensified radiation therapy regimens but was associated with >90% rates of ulceration of the anterior rectal wall on endoscopic assessment; this infrequently progressed to severe rectal toxicity in prior prospective series. A multi-institutional phase 2 prospective trial was conducted to assess whether placement of a perirectal hydrogel spacer would reduce acute periprostatic rectal ulcer events after high-dose (>40 Gy) SABR. METHODS AND MATERIALS: Eligible patients included men with stage ≤T2c localized grade group 1 to 3 prostate cancer, a prostate-specific antigen (PSA) level ≤15 ng/mL, American Urological Association Symptom Index = AUA-SI scores ≤18, and a gland volume ≤80 cm3. Patients underwent perirectal hydrogel spacer placement, followed by SABR of 45 Gy in 5 fractions every other day to the prostate only. Androgen deprivation was not allowed except for cytoreduction. The rectal wall was directly assessed by serial anoscopy during follow-up to determine whether the spacer would reduce acute periprostatic rectal ulcer events from >90% to <70% within 9 months of treatment. RESULTS: Forty-four men were enrolled and 43 were eligible for protocol analysis. The median follow-up for surviving patients was 48 months. Acute periprostatic ulcers were observed in 6 of 42 patients (14.3%; 95% confidence interval, 6.0%-27%; P < .001) at a median of 2.9 months posttreatment (range, 1.7-5.6 months). All ulcers (grade 1, 5 ulcers; grade 2, 1 ulcer) resolved on repeat anoscopy within 8 months of incidence. There were no grade ≥3 late gastrointestinal toxicities; the incidence of late grade-2 gastrointestinal toxicities was 14.3%, with a prevalence at 3 years of 0%. No toxicities greater than grade 3 occurred in any domain. Four-year freedom from biochemical failure was 93.8% (95% CI, 85.2%-100.0%). CONCLUSIONS: Temporary hydrogel spacer placement before high-dose SABR treatment for localized prostate cancer and use of strict dose constraints are associated with a significant reduction in the incidence of rectal ulcer events compared with prior phase 1/2 trial results.

Trends and Factors Associated With Receipt of Upfront Surgery for Stage II to III Rectal Adenocarcinoma in the United States, 2006 to 2016.

INTRODUCTION: The German rectal study published in 2004 established neoadjuvant chemoradiation as a standard of care for locally advanced rectal cancer and current National Comprehensive Cancer Network guidelines endorse several preoperative regimens. Upfront surgery, however, is considered substandard care. In the era of evolving treatment paradigms for locally advanced rectal cancer, we sought to assess trends and predictors of receipt of upfront surgery for stage II to III rectal cancer. METHODS: The National Cancer Database was used to identify patients diagnosed with clinical stage II to III rectal adenocarcinoma between 2006 and 2016. Multivariable logistic regression defined adjusted odds ratios and associated 95% confidence intervals of receipt of upfront definitive surgery. The timing of upfront surgery relative to day of diagnosis and rate of receipt of adjuvant therapy were also estimated. RESULTS: Among 51,562 patients, 6411 (12.4%) were treated with upfront surgery, which decreased from 16.7% in 2006 to 7.1% in 2016 (P<0.001). The majority of patients (5737 [89.5%]) had definitive surgery after initial diagnostic biopsy. Variables associated with receipt of upfront surgery included female sex, older age, higher comorbidity score, and treatment at a community cancer center (P<0.001). Among those receiving upfront surgery, 2904 (45.3%) received adjuvant radiation therapy, 3218 (50.2%) received adjuvant chemotherapy, and 2559 (39.9%) received no further treatment. CONCLUSIONS: The proportion of patients with clinical stage II to III rectal cancer treated with upfront surgery has steadily declined since 2006, however, certain subgroups appear to remain at greater risk. Further research is needed to better elucidate patient and systems-level factors contributing to these disparities in care.

Patterns of Dose Escalation Among Patients With Esophageal Cancer Undergoing Definitive Radiation Therapy: 2006-2016.

PURPOSE: Although single-institution series suggest potential benefit to dose escalation in definitive radiation therapy for esophageal cancer, randomized trials including intergroup-0123 and the recently presented A Randomized Trial of Dose Escalation in definitive Chemoradiotherapy for patients with Oesophageal cancer (ARTDECO) trial showed no improvement in outcomes with higher radiation therapy dose. As such, there may be significant variation in radiation dose for definitive treatment of esophageal cancer. METHODS AND MATERIALS: The National Cancer Database was used to identify patients who received a diagnosis of nonmetastatic T2+ esophageal cancer between 2006 and 2016 who did not receive definitive surgery and were treated with chemotherapy and radiation therapy doses between 41.4 and 74 Gy. Multivariable logistic regression defined adjusted odds ratios (AORs) of receipt of >50.4 Gy, including year of diagnosis (2006-2013 vs 2014-2016) ∗ histology (squamous cell carcinoma [SCC] vs adenocarcinoma) and year of diagnosis (2006-2013 vs 2014-2016) ∗ disease site (cervical esophagus vs noncervical esophagus) interaction terms, to assess whether the effect of diagnosis year on dose varied by histology and disease site, respectively. RESULTS: Among 14,517 patients, the most common dose was 50.4 Gy, used for 6955 (47.9%) patients. Dose escalation above 50.4 Gy was observed in 4440 (30.6%) patients and declined by year, from 42.2% in 2006 to 23.5% in 2016. Patients with SCC versus adenocarcinoma had higher odds of dose escalation (39.3% vs 23.8%; AOR 1.46; P < .001), as did those with cervical esophageal primaries versus other primary sites (54.9% vs 27.4%; AOR 2.51; P < .001). The effect of later diagnosis year was greater for adenocarcinoma than for SCC (pint = 0.001, AOR 0.54, P < .001 vs AOR 0.71, P < .001) and significant for noncervical esophagus but not cervical esophagus (pint <0.001, AOR 0.56, P < .001 vs AOR 0.95, P = .616). CONCLUSIONS: Dose escalation in definitive chemoradiotherapy for esophageal cancer declined over time, particularly for adenocarcinoma histology and noncervical primary site. Given the recent results of ARTDECO, our findings can serve as a benchmark from which to measure future shifts in practice patterns.

Disparities in Characteristics, Access to Care, and Oncologic Outcomes in Young-Onset Colorectal Cancer at a Safety-Net Hospital.

PURPOSE: Young-onset colorectal cancer is an emerging cause of significant morbidity and mortality globally. Despite this, limited data exist regarding clinical characteristics and outcomes, particularly in safety-net populations where access to care is limited. We aimed to study disparities in clinical characteristics and outcomes in patients with young-onset colorectal cancer in the safety-net setting. METHODS: We performed a retrospective review of patients < 50 years old diagnosed and/or treated for colorectal cancer between 2001 and 2017 at a safety-net hospital. Kaplan-Meier and Cox regression models were constructed to compare overall survival (OS), progression-free survival (PFS), and relapse-free survival (RFS) by race and ethnicity, stratifying for relevant clinical and pathologic factors. RESULTS: A total of 395 young-onset patients diagnosed at a safety-net hospital were identified and 270 were included in the analysis (49.6% Hispanic, 25.9% non-Hispanic Black, 20.0% non-Hispanic White, and 4.4% other). Non-Hispanic White race was independently associated with worse OS (hazzard ratio [HR], 0.53; 95% CI, 0.29 to 0.97), as were lack of insurance, higher clinical stage, and mismatch repair proficiency. There was no significant difference seen in PFS or RFS between racial and ethnic groups. CONCLUSION: Non-Hispanic White race or ethnicity was found to be independently associated with worse OS in a safety-net population of patients with young-onset colorectal cancer. Other independent predictors of worse OS include higher stage, lack of insurance, and mismatch repair proficiency.

Long-Term Results of a Phase 1 Dose-Escalation Trial and Subsequent Institutional Experience of Single-Fraction Stereotactic Ablative Radiation Therapy for Liver Metastases.

PURPOSE: We report long-term outcomes from our phase 1 dose-escalation study to determine the maximum tolerated dose of single-fraction liver SABR pooled with our subsequent single institutional experience with patients treated postprotocol at the highest dose level (40 Gy) established from the phase 1 study. METHODS AND MATERIALS: Patients with liver metastases from solid tumors located outside of the central liver zone were treated with single-fraction SABR on a phase 1 dose escalation trial. At least 700 cc of normal liver had to receive <9.1 Gy. Seven patients with 10 liver metastases received the initial prescription dose of 35 Gy, and dose was then escalated to 40 Gy for 7 more patients with 7 liver metastases. An additional 19 postprotocol patients with 22 liver metastases were treated to 40 Gy in a single fraction. Patients were followed for toxicity and underwent serial imaging to assess local control. RESULTS: Median imaging follow-up for the combined cohort (n = 33, 39 lesions) was 25.9 months; 38.9 months for protocol patients and 20.2 months for postprotocol patients. Median lesion size was 2.0 cm (range, 0.5-5.0 cm). There were no dose-limiting toxicities observed for protocol patients, and only 3 grade 2 toxicities were observed in the entire cohort, with no grade ≥3 toxicities attributable to treatment. Four-year actuarial local control of irradiated lesions in the entire cohort was 96.6%, 100% in the protocol group and 92.9% in the subsequent patients. Two-year overall survival for all treated patients was 82.0%. CONCLUSIONS: For selected patients with liver metastases, single-fraction SABR at doses of 35 and 40 Gy was safe and well-tolerated, and shows excellent local control with long-term follow-up; results in subsequent patients treated with single-fraction SABR doses of 40 Gy confirmed our earlier results.

Review of brachytherapy complications - Upper gastrointestinal tract.

While brachytherapy applications are not widely used for cancer diagnoses in the upper GI tract (including the esophagus, liver, stomach, and pancreas), they have a clear role in palliation and symptom management and occasionally definitive locoregional treatment. With the increasing use of image-guided techniques, the incidence of side effects and complications has shown to be lower than many other alternative treatment modalities, making brachytherapy approaches a preferred treatment option. This review examines procedural complications and acute and chronic adverse effects from radiation associated with esophageal, hepatobiliary, and pancreatic brachytherapy and their management.

Quantitative PET Imaging and Clinical Parameters as Predictive Factors for Patients With Cervical Carcinoma: Implications of a Prediction Model Generated Using Multi-Objective Support Vector Machine Learning.

PURPOSE: Quantitative features from pre-treatment positron emission tomography (PET) have been used to predict treatment outcomes for patients with cervical carcinoma. The purpose of this study is to use quantitative PET imaging features and clinical parameters to construct a multi-objective machine learning predictive model. MATERIALS/METHODS: Seventy-five patients with stage IB2-IVA disease treated at our institution from 2009-2012 were analyzed. Models predicting locoregional and distant failure were generated using clinical parameters (age, race, stage, histology, tumor size, nodal status) and imaging features (12 textural, 9 intensity, 8 geometric features, 2 additional imaging features) from pre-treatment PET. Model features were selected based on a multi-objective evolutionary algorithm to maximize specificity given a fixed moderately high sensitivity using support vector machine learning methods. Model 1 used clinical parameters only (C), Model 2 used imaging features only (I), and Model 3 used clinical and imaging features (C+I). Sensitivity, specificity, area under a receiver-operating characteristic curve (AUC), and p-values were compared to assess ability to predict locoregional and distant failure. RESULTS: C+I had the highest performance for both locoregional failure (AUC 0.84, p < 0.01; specificity: 0.86; sensitivity: 0.79) and distant failure (AUC 0.75, p < 0.01; specificity: 0.75; sensitivity: 0.75). CONCLUSIONS: Based on a moderately high fixed sensitivity and optimized for specificity, the model using both clinical parameters and imaging features (C+I) had the best performance in predicting both locoregional failure and distant failure.

Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016.

BACKGROUND: When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC. METHODS: Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression. RESULTS: Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P<0.0001; absolute percentage: 62.3% to 43.8%). Similar trends by year for PTR were observed among each of the subgroups, although patients with colon primary, young adults (age younger than 50 y), and patients also undergoing metastasectomy were more likely to undergo PTR (P<0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with a later year of diagnosis (adjusted odds ratio=2.21, 95% confidence interval: 2.04-2.40, P<0.0001). CONCLUSIONS: From 2000 to 2016, there was a sharp decline in the rate of PTR for patients with metastatic CRC, while the use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC.