Improved survival with combination chemotherapy and external beam radiation therapy in uterine carcinosarcoma.

OBJECTIVES: To evaluate differences in survival and recurrence patterns in stage I-IV uterine carcinosarcoma patients treated with surgery followed by adjuvant chemotherapy alone, radiation alone, or a combination of both chemotherapy and radiation therapy. METHODS: A multicenter retrospective analysis of patients with surgically staged carcinosarcoma receiving adjuvant therapy from January 2000 to December 2019 was conducted. Inclusion criteria were patients with carcinosarcoma who had received primary surgical treatment, followed by adjuvant therapy with chemotherapy alone, radiation therapy alone, or a combination of chemoradiation. Patients were excluded for incomplete surgical staging data, adjuvant brachytherapy alone, adjuvant chemotherapy and brachytherapy without external beam radiation therapy, receipt of neoadjuvant chemotherapy and/or pre-operative pelvic radiation, and death due to non-cancer causes. Sites of recurrence were analyzed by adjuvant treatment modality using Pearson's χ2 test. Progression-free and overall survival were calculated using Kaplan-Meier estimates. Multivariate analysis was performed using Cox proportional hazards model. RESULTS: Of 176 evaluable patients, 27% (n=47) had stage I, 14% (n=24) stage II, 37% (n=66) stage III, and 22% (n=39) stage IV disease. Among them, 33% (n=59) received chemotherapy alone, 17% (n=29) received radiation therapy alone, and 50% (n=88) received chemoradiation. Patients with stage I disease recurred less frequently (64%) versus stage II (83%), stage III (85%), and stage IV (90%) (p<0.001). Stage I disease demonstrated improved progression-free and overall survival relative to all other stages (p<0.01). Across all stages, patients receiving chemoradiation experienced superior progression-free (p=0.01) and overall survival (p=0.05) versus single modality therapy. However, when analyzed in a stage-specific manor, stage III disease derived the greatest survival benefit from chemoradiation versus all other stages (p<0.01). On multivariant analysis, only stage and receipt of chemoradiation were independent predictors of survival. CONCLUSION: Stage I disease demonstrated improved survival compared with other stages regardless of adjuvant treatment modality. Chemoradiation was associated with improved survival and better distant and local disease control for all stages of disease. Patients with stage III disease derived the most benefit from chemoradiation.

Atypical ductal hyperplasia on core needle biopsy: Surgical outcomes of 200 consecutive cases from a high-volume breast program.

Atypical ductal hyperplasia (ADH) is an indication for excisional biopsy to rule out occult breast cancer. We analyzed pathological findings on excisional biopsy for ADH diagnosed in a high volume breast center equipped with digital tomosynthesis. Two hundred consecutive patients were diagnosed with ADH on core biopsy with radiographic concordance followed by excisional biopsy. On excisional biopsy, 33 patients (16.5%) were diagnosed with DCIS or invasive breast cancer. Patients with a concurrent diagnosis of papilloma had a higher risk of upstaging on both univariate and multivariate analysis (41.7% vs. 14.9%, p=0.015). No other statistically significant predictors of upgrading were identified (p>0.05).

Atypical lobular hyperplasia on core needle biopsy: contemporary results from a large community hospital breast program.

PURPOSE: The management of biopsy proven atypical lobular hyperplasia (ALH) is controversial. Although upgrade rates are low, excisional biopsy is often performed to rule out occult breast cancer. METHODS: In this study, we analyzed our experience with excisional biopsy for ALH diagnosed in the digital tomosynthesis era with radiographic concordance in the community hospital setting. This study included 93 consecutive patients diagnosed with pure ALH on core biopsy from January 2013-December 2017 who underwent subsequent excisional biopsy. Potential clinical, radiographic and pathologic predictors of upgrading were analyzed. RESULTS: At the time of excisional biopsy, five patients (5.4%) were upgraded to DCIS or invasive breast cancer. There was also a trend towards higher upgrade rates in patients with contralateral breast cancer (p = 0.06), biopsy performed by ultrasound or MRI (p = 0.07) and extensive ALH (p = 0.10). Other clinical, radiographic and pathologic variables were not predictive of upgrade rate (p > 0.1 for all). CONCLUSION: Patients with pure ALH with radiographic concordance have a low risk of pathologic upgrading on excisional biopsy. Potential predictors of upgrade rate warrant further analysis in a larger dataset.

Predicting long­term survival following involved site radiotherapy for oligometastases.

The majority of cancer-associated mortalities are due to distant metastases, and systemic therapy alone is generally not curative. Patients with oligometastases are amenable to involved site radiotherapy with the possibility of long-term disease-free survival; however, prognostic factors remain poorly defined. The present retrospective, single institution study consisted of consecutive adult patients with oligometastases from solid tumor malignancy referred to a single high volume radiation oncologist between January 2014 and December 2021. Oligometastases were defined as ≤5 extracranial or intracranial metastatic lesions where all sites of active disease are treatable, including patients requiring treatment of the primary tumor and/or regional lymph nodes. The study population consisted of 130 patients with 207 treated distant metastases. Radical radiotherapy was administered to all areas of known residual disease and included stereotactic radiotherapy (median dose, 27 Gy in 3 fractions) or intensity modulated radiotherapy (median dose, 50 Gy in 15 fractions). At a median follow-up of 28.8 months, the median overall survival was 37.9 months with a 4-year overall survival of 41.1%. The median progression-free survival was 12.3 months and the 4-year progression-free survival was 22.6%. On multivariate an1alysis, the strongest predictors of overall survival were age, ECOG performance status, primary prostate, breast or kidney tumor and pre-radiation serum albumin (P≤0.01 for all). Overall, the present study demonstrated that long-term overall survival was possible after radical treatment for oligometastases and identified potential prognostic factors.

Long-term disease-free survival following comprehensive involved site radiotherapy for oligometastases.

Introduction: Despite recent advances in drug development, durable complete remissions with systemic therapy alone for metastatic cancers remain infrequent. With the development of advanced radiation technologies capable of selectively sparing normal tissues, patients with oligometastases are often amenable to comprehensive involved site radiotherapy with curative intent. This study reports the long-term outcomes and patterns of failure for patients treated with total metastatic ablation often in combination with systemic therapy. Materials and methods: Consecutive adult patients with oligometastases from solid tumor malignancy treated by a single high volume radiation oncologist between 2014 and 2021 were retrospectively analyzed. Oligometastases were defined as 5 or fewer metastatic lesions where all sites of active disease are amenable to local treatment. Comprehensive involved site radiotherapy consisted of stereotactic radiotherapy to a median dose of 27 Gy in 3 fractions and intensity modulated radiation therapy to a median dose of 50 Gy in 15 fractions. This study analyzed overall survival, progression-free survival, patterns of failure and toxicity. Results: A total of 130 patients with 209 treated distant metastases were treated with a median follow-up of 36 months. The 4-year overall survival, progression-free survival, local control and distant control was 41%, 23%, 86% and 29%. Patterns of failure include 23% alive and free of disease (NED), 52% distant failure only, 9% NED but death from comorbid illness, 7% both local and distant failure, 4% NED but lost to follow-up, 4% referred to hospice before restaging, 1% local only failure, 1% alive with second primary cancer. Late grade 3+ toxicities occurred in 4% of patients, most commonly radionecrosis. Conclusion: Involved site radiotherapy to all areas of known disease can safely achieve durable complete remissions in patients with oligometastases treated in the real world setting. Distant failures account for the majority of treatment failures and isolated local failures are exceedingly uncommon. Oligometastases represents a promising setting to investigate novel therapeutics targeting minimal residual disease.

Personalized Palliative and Survivorship Care for Patients With Metastatic Cancer Treated With Radiation Therapy.

While the benefits of early palliative care for patients with metastatic cancer are well established, cancer survivorship remains inadequately integrated into the care of patients with distant metastases. Moreover, the optimal model of care delivery is poorly defined. A prognostic model previously developed and validated at Good Samaritan University Hospital identified four groups of patients with metastatic solid tumor malignancy having very favorable, favorable, standard or unfavorable prognoses with median survival of 31, 14, 4 and 1 month, respectively. This framework holds promise for the personalized delivery of supportive, palliative and survivorship care services in the context of radiation therapy. We review the published literature providing the rationale for a novel multidisciplinary care model where the radiation oncology Clinical Nurse Specialist identifies and coordinates interventions to address unmet physical and emotional issues faced by survivors with metastatic cancer with the goal of improving quality of life and overall survival.

Improving Survival Prognostication in Patients With Metastatic Cancer Through Clinical Judgment.

BACKGROUND/AIM: NEAT is a validated prognostic model that calculates survival estimates based on the number of active tumors, ECOG performance status, albumin, and primary tumor site. Since models are imperfect, we hypothesized that experienced clinicians could predict the survival of patients with metastatic cancer better than a validated prognostic model alone, thereby quantifying the previously unmeasured value of clinical judgment. PATIENTS AND METHODS: This prospective, single-institution cohort study conducted at a large community hospital recruited 73 patients with metastatic cancer referred to radiation oncology between October 2016 and December 2017. The consulting nurse and physician were prospectively surveyed on whether the patient would survive a longer or shorter duration than the calculated NEAT survival estimates. The accuracy of predictions between groups was assessed using the McNemar's chi-squared test. RESULTS: The median survival for enrolled patients was 9.2 months. Nursing and physician predictions were similarly accurate (61.6% vs. 60.3%, p=0.85). The accuracy of confident clinical predictions was similar to less confident predictions (64.2% vs. 58.2%, p=0.46). Radiation dose intensity was informed by predicted survival, and median survival was significantly higher in patients receiving an EQD2≥40 (17 months vs. 2 months, p<0.001). CONCLUSION: Experienced clinicians, both nurses and oncologists, have insight that modestly supplements the accuracy of a validated model to predict survival in patients with advanced cancer.

Phase 1 trial of concurrent erlotinib, celecoxib, and reirradiation for recurrent head and neck cancer.

BACKGROUND: Concurrent inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) is an active and well tolerated regimen in recurrent head and neck cancer (HNC). In the current phase 1 trial, the authors sought to determine the maximum tolerated dose (MTD) and efficacy of concurrent erlotinib and celecoxib as a radiosensitizing regimen. METHODS: Fourteen patients with previously irradiated HNC with no distant metastases who required reirradiation were eligible. Treatment consisted of daily erlotinib 150 mg and twice daily celecoxib (escalated from 200 mg to 600 mg using a 3 + 3 design with an expanded cohort at the MTD) starting on Day 1 and was continued during radiation. Daily radiation was started on Day 15, and maintenance erlotinib was recommended. RESULTS: The recommended phase 2 dose of celecoxib was 400 mg. Three dose-limiting toxicities included late in-field orocutaneous fistula (Dose Level 2), osteonecrosis (Dose Level 3), and trismus (Dose Level 3). Acute grade ≥ 3 toxicities were uncommon and included mucositis (21%) and dermatitis (14%). At a median follow-up of 11 months, the 1-year locoregional control, progression-free survival, and overall survival rates were 60%, 37%, and 55%, respectively. CONCLUSIONS: Concurrent erlotinib, celecoxib, and reirradiation was a feasible and clinically active regimen in a population of patients with recurrent HNC who had a poor prognosis.

Cancers of the oral cavity and oropharynx: FDG PET with contrast-enhanced CT in the posttreatment setting.

The combined use of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and contrast material-enhanced computed tomography (CT) for posttreatment monitoring of cancers of the oral cavity and oropharynx has steadily increased in recent years. FDG PET/CT offers many advantages for evaluating the effects of therapy, determining whether residual or recurrent disease is present, and assessing the extent of nodal disease. Because of the high negative predictive value of this imaging test, some have advocated the deferral of neck dissection in patients with negative findings at FDG PET/CT after chemotherapy and radiation therapy; positive findings may have a similarly heavy influence on the future course of treatment. Thus, the accuracy of image interpretation is crucial. However, the interpretation of posttreatment FDG PET images is challenging, with multiple potential pitfalls and limitations that could lead to an incorrect analysis. Accuracy depends on a detailed knowledge of the patient's treatment history and a thorough understanding of the kinds of changes that might result from treatment. Awareness of the principles underlying the selection of the optimal interval between the completion of treatment and the first follow-up FDG PET/CT examination is especially important, since an interval that is too short could lead to false-positive or false-negative findings. A period of 12 weeks or more is generally recommended, but the optimal waiting period depends on the extent of therapy and other factors. If recurrence or progression is suspected during the waiting period, contrast-enhanced CT or magnetic resonance imaging should be performed without FDG PET.

Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity.

Current research in prostate brachytherapy focuses on five key concepts covered in this review. Transrectal ultrasound-guided prostate brachytherapy assisted by intraoperative treatment planning is the most advanced form of image-guided radiation delivery. Prostate brachytherapy alone for low-risk prostate cancer achieves lower prostate-specific antigen (PSA) nadirs than intensity-modulated radiotherapy (IMRT) or protons while maintaining durable biochemical control in about 90% of patients without late failures seen in surgically treated patients. As an organ-conserving treatment option, seed implant results in a lower rate of erectile dysfunction and urinary incontinence than surgery that has been validated in several recent prospective studies. Combined IMRT and seed implant has emerged as a rational and highly effective approach to radiation-dose escalation for intermediate- and high-risk prostate cancer. Preliminary results suggest that seed implantation may play a role in improving outcomes for historically poor-prognosis locally advanced and recurrent prostate cancers.

Association of radiation dose intensity with overall survival in patients with distant metastases.

BACKGROUND: Patients with metastatic cancer referred to radiation oncology have diverse prognoses and there is significant interest in personalizing treatment. We hypothesized that patients selected for higher biologically equivalent doses have improved overall survival. METHODS: The study population consists of 355 consecutive adult patients with distant metastases treated by a single radiation oncologist from 2014 to 2018. The validated NEAT model was used to prospectively stratify patients into four distinct cohorts. Radiation dose intensity was standardized using the equivalent dose in 2 Gy fractions (EQD2) model with an α/ß of 10. Radiation dose intensity on survival was assessed via Cox regression models and propensity score match pairing with Kaplan-Meier analysis. RESULTS: The median survival was 9.3 months and the median follow-up for surviving patients was 18.3 months. The NEAT model cohorts indicated median survivals of 29.5, 11.8, 4.9, and 1.8 months. Patients receiving an EQD2 of ≥40 Gy had a median survival of 16.0 months versus 3.8 months for patients receiving an EQD2 of <40 Gy (p < 0.001). On multivariable analysis, performance status, primary tumor site, radiation dose intensity, albumin, liver metastases, and number of active tumors were all independent predictors of survival (p < 0.05 for all). Propensity score matching was performed for performance status, albumin, number of active tumors, primary tumor site, and liver metastasis, finding higher EQD2 to remain significantly associated with improved survival within the matched cohort (p = 0.004). CONCLUSION: Higher radiation dose intensity was used in patients with better prognosis and was associated with improved survival for patients with metastatic disease.

FDG PET with contrast-enhanced CT: a critical imaging tool for laryngeal carcinoma.

Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has evolved to be an essential imaging modality in the evaluation of laryngeal carcinoma. Although the modality has limited utility in assessing the extent of the primary tumor, FDG PET has proved to be superior to anatomic modalities in the detection of lymph node and distant metastases. The role of FDG PET in the evaluation of patients with laryngeal tumors that are clinically classified as N0 has not shown consistent usefulness because of the innate resolution limitations of the camera. In the posttherapy setting, however, FDG PET has consistently demonstrated a high negative predictive value in the identification of recurrent disease, both during the course of therapy and during long-term follow-up. In addition, contrast material-enhanced computed tomography (CT) in conjunction with FDG PET has demonstrated a complementary role by allowing for superior anatomic coregistration and therefore more definitive diagnosis. There is sufficient evidence that with further advances in PET technology, this modality will likely become more useful in the detection of small lesions and occult nodal disease, as well as in guiding the management of laryngeal carcinoma.

Multiparametric prostate MRI-based intensity-modulated radiation therapy guided by prostatic calcifications.

OBJECTIVES: The optimal technique to administer image-guided radiation therapy for prostate cancer remains poorly defined. This study assessed outcomes after multiparametric prostate MRI-based planning was delivered with image-guided radiation therapy using prostatic calculi observed on cone beam CT (CBCT). METHODS: Between January 2015 and December 2017, 94 consecutive patients were treated with CBCT-based image-guided radiation therapy (IGRT) without fiducial markers. MRI was routinely incorporated for target delineation and intraprostatic tumor nodules were boosted to allow reduced doses to normal appearing prostate. The primary endpoint was the prevalence of prostatic calcifications while toxicity and biochemical control were secondary endpoints. RESULTS: Median follow-up was 39.7 months with 82% NCCN intermediate to very high risk. Intraprostatic calculi were noted in 68% of patients. The 3-year biochemical control, late grade ≥2 rectal toxicity and late grade ≥2 urinary toxicity rates were 96%, 3 and 7%, respectively. Biochemical control and toxicity were not significantly impacted by the presence of prostatic calculi. CONCLUSION: Prostatic calcifications can serve as natural fiducial markers to allow for non-invasive IGRT for prostate cancer with promising early disease control and toxicity outcomes. ADVANCES IN KNOWLEDGE: Prostate calcification-guided IGRT is technically feasible.

Prognostic role of baseline neutrophil-to-lymphocyte ratio in metastatic solid tumors.

High baseline neutrophil-to-lymphocyte ratio (NLR) has been associated with poor survival in a number of solid tumors, but has not been extensively investigated in the context of radiation oncology. Developing more robust models to predict survival would inform patient care for patients with metastatic solid tumors. The present study was undertaken to evaluate the effect of baseline NLR (using 4 as a cutoff) on survival in 320 consecutive patients with metastatic cancer who were referred to a single radiation oncologist between 2012 and 2015, with a median follow-up of 20.6 months. The median NLR was 4.4 (interquartile range, 2.8-7.2). Patients with a baseline NLR ≤4 had a median survival of 9.3 months compared to 4.1 months for NLR >4 (P<0.001). The number of active tumors, Eastern Cooperative Oncology Group performance status score, baseline albumin, primary tumor site, liver metastases and baseline NLR predicted overall survival on both univariate and multivariate analysis (P<0.05 for all). After adjusting for known prognostic factors for advanced solid tumors, baseline NLR >4 independently predicted adverse survival in this cohort.

Development of an automated gamma-H2AX immunocytochemistry assay.

gamma-H2AX is emerging as an important marker of ionizing radiation-induced double-strand breaks. Development of a significantly automated method to quantify gamma-H2AX would have broad application in assessing physiological responses to radiation exposure. PC-3 and DU145 prostate cancer cells grown on glass cover slips and 96-well plates were irradiated and assessed for gamma-H2AX focus formation by immunofluorescence analysis. The gamma-H2AX immunofluorescence staining was performed either manually or by using a preprogrammed automated robotic liquid handling system. A computer-controlled charge-coupled device camera acquired images serially throughout the thickness of each cell. Image analysis was performed manually and/or with automated image segmentation software. A robust relationship between radiation dose and gamma-H2AX focus numbers was demonstrated with both manual and automated image analysis methods, with excellent agreement observed between the two techniques. The r(2) correlation coefficients and Z factors exceeded 0.9 and 0.5, respectively, when gamma-H2AX focus formation was correlated with radiation dose using the automated technique. Inhibition of gamma-H2AX foci by drugs readily detected with this assay. Robotic specimen preparation with automated image acquisition and analysis can be used to quantify gamma-H2AX foci in irradiated cells, and the results agree well those obtained by manual counts. These data suggest that this assay has an excellent signal-to-noise ratio and is suitable for high-throughput applications.

Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage.

PURPOSE: Adjuvant radiotherapy (RT) is frequently recommended for node-positive head and neck squamous cell carcinoma (HNSCC) treated with primary surgery. The impact of RT on survival for various subgroups of node-positive HNSCC has not been clearly demonstrated. METHODS AND MATERIALS: Within the Surveillance, Epidemiology, and End Results (SEER) Database, we identified 5297 patients with node-positive (N1 to N3) HNSCC treated with definitive surgery with or without adjuvant RT between 1988 and 2001. The median follow-up was 4.4 years. RESULTS: Adjuvant RT significantly improved 5-year overall survival (46.3%: 95% confidence interval [CI], 44.7-48.0% for surgery + RT, vs. 35.2%: 95% CI, 32.0-38.5% for surgery alone, p < 0.001) and cancer-specific survival (54.8%: 95% CI, 53.2-56.4% for surgery + RT, vs. 46.2% for surgery alone 95% CI, 42.4-50.0%, p < 0.05). Use of adjuvant RT remained a significant predictor of survival on multivariable analysis (hazard ratio [HR], 0.75; 95% CI, 0.68-0.83; p < 0.001). Subset analyses demonstrated that adjuvant RT was associated with significantly improved survival for N1 (HR, 0.78; 95% CI; 0.67-0.90; p = 0.001), N2a (HR, 0.82; 95% CI, 0.67-0.99, p = 0.048) and N2b to N3 nodal disease (HR, 0.62; 95% CI, 0.51-0.75; p < 0.001). Adjuvant RT increased overall survival for node-positive patients with oropharynx (HR, 0.72; 95% CI, 0.57-0.90; p = 0.004), hypopharynx (HR, 0.66; 95% CI, 0.49 to 0.88; p = 0.004), larynx (HR, 0.66; 95% CI, 0.52-0.84; p = 0.001), and oral cavity (HR, 0.84; 95% CI, 0.73-0.98; p = 0.025) primary tumors. CONCLUSIONS: In a large population-based analysis, adjuvant RT significantly improves overall survival for patients with node-positive HNSCC. All nodal stages, including N1, appear to benefit from the addition of RT to definitive surgery.

Correlation of positron emission tomography standard uptake value and pathologic specimen size in cancer of the head and neck.

PURPOSE: To correlate positron emission tomography (PET) standard uptake value (SUV) with pathologic specimen size in patients with head-and-neck cancers. METHODS AND MATERIALS: Eighteen patients with Stage II-IVB head-and-neck cancer with 27 tumors who underwent PET and computed tomography (CT) imaging of the head and neck followed by surgical resection were selected for this study. Various SUV thresholds were examined, including the software default (SUV(def)), narrowing the window by 1 standard deviation (SD) of the maximum (SUV-1SD), and SUV cutoff values of 2.5 or greater (SUV2.5) and 40% or greater maximum (SUV40). Volumetric pathologic data were available for 12 patients. Tumor volumes based on pathologic examination (gold standard), CT, SUV(def), SUV-1SD, SUV2.5, and SUV40 were analyzed. RESULTS: PET identified five tumors not seen on CT. The sensitivity of PET for identifying primary tumors was 94% (17 of 18). The Sensitivity of PET for staging the neck was 90% (9 of 10), whereas the specificity was 78% (7 of 9). The SUV2.5 method was most likely to overestimate tumor volume, whereas SUV(def) and SUV-1SD were most likely to underestimate tumor volume. CONCLUSIONS: The PET scan provides more accurate staging of primary tumors and nodal metastases for patients with advanced head-and-neck cancer than CT alone. Compared with the gold standard, significant variability exists in volumes obtained by using various SUV thresholds. A combination of clinical, CT, and PET data should continue to be used for optimal treatment planning. The SUV40 method appears to offer the best compromise between accuracy and reducing the risk of underestimating tumor extent.

(125)I monotherapy using D90 implant doses of 180 Gy or greater.

PURPOSE: The purpose of this study was to characterize the oncologic results and toxicity profile of patients treated with (125)I implants using the dose delivered to 90% of the gland from the dose-volume histogram (D90) of greater than 144 Gy. METHODS AND MATERIALS: From June 1995 to Feb 2005, a total of 643 patients were treated with (125)I monotherapy for T1-T2 prostate cancer with a D90 of 180 Gy or greater (median, 197 Gy; range, 180-267 Gy). Implantations were performed using a real-time ultrasound-guided seed-placement method and intraoperative dosimetry to optimize target coverage and homogeneity by using modified peripheral loading. We analyzed biochemical disease-free survival (bDFS) of 435 patients who had a minimum 2-year prostate-specific antigen follow-up (median follow-up, 6.7 years; range, 2.0-11.1 years). RESULTS: Five-year bDFS rates for the entire cohort using the American Society for Therapeutic Radiology and Oncology and Phoenix definitions were 96.9% and 96.5%, respectively. Using the Phoenix definition, 5-year bDFS rates were 97.3% for low-risk patients and 92.8% for intermediate/high-risk patients. The positive biopsy rate was 4.1%. The freedom rate from Grade 2 or higher rectal bleeding at 5 years was 88.5%. Acute urinary retention occurred in 10.7%, more commonly in patients with high pretreatment International Prostate Symptom Scores (p < 0.01). In patients who were potent before treatment, 73.4% remained potent at 5 years after implantation. CONCLUSIONS: Patients with a minimum D90 of 180 Gy had outstanding local control based on prostate-specific antigen control and biopsy data. Toxicity profiles, particularly for long-term urinary and sexual function, were excellent and showed that D90 doses of 180 Gy or greater performed using the technique described were feasible and tolerable.

The NEAT Predictive Model for Survival in Patients with Advanced Cancer.

PURPOSE: We previously developed a model to more accurately predict life expectancy for stage IV cancer patients referred to radiation oncology. The goals of this study are to validate this model and to compare competing published models. MATERIALS AND METHODS: From May 2012 to March 2015, 280 consecutive patientswith stage IV cancerwere prospectively evaluated by a single radiation oncologist. Patients were separated into training, validation and combined sets. TheNEAT model evaluated number of active tumors ("N"), Eastern Cooperative Oncology Group performance status ("E"), albumin ("A") and primary tumor site ("T"). The Odette Cancer Center model validated performance status, bone only metastases and primary tumor site. The Harvard TEACHH model investigated primary tumor type, performance status, age, prior chemotherapy courses, liver metastases, and hospitalization within 3 months. Cox multivariable analyses and logisticalregressionwere utilized to compare model performance. RESULTS: Number of active tumors, performance status, albumin, primary tumor site, prior hospitalizationwithin the last 3 months, and liver metastases predicted overall survival on uinvariate and multivariable analysis (p < 0.05 for all). The NEAT model separated patients into four prognostic groups with median survivals of 24.9, 14.8, 4.0, and 1.2 months, respectively (p < 0.001). The NEAT model had a C-index of 0.76 with a Nagelkerke's R2 of 0.54 suggesting good discrimination, calibration and total performance compared to competing prognostic models. CONCLUSION: The NEAT model warrants further investigation as a clinically useful approach to predict survival in patients with stage IV cancer.

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis.

BACKGROUND: Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT). METHODS: Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors. RESULTS: 361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS. CONCLUSIONS: We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.