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.

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.

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.

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.

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).

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.

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.

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.

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.

Effect of modern, high-quality prostate intensity-modulated radiation therapy on outcome: Evidence from a community radiation oncology program.

Radiation technique for prostate cancer has continuously evolved over the past several decades. The aim of the present study was to describe the effects of implementing modern prostate intensity-modulated radiation therapy (M-IMRT) on dosimetry and outcome. Between January 2010 and April 2012, 48 consecutive patients were treated with conventional prostate IMRT (C-IMRT) to a dose of 81 Gy. Between May 2012 and April 2015, 50 consecutive patients were treated with M-IMRT to the entire prostate to a dose of 75.6-79.2 Gy, while using prostate magnetic resonance imaging fusion, dose-volume constraints prioritizing normal tissue avoidance above planning target volume coverage, and boosting any dominant intraprostatic masses to 79.2-81 Gy. Rectal Dmax, V75, V60, V65 and V50, bladder Dmax, V75, V70 and V65, and acute and late toxicities were compared between the C-IMRT and M-IMRT groups. The median follow-up for the C-IMRT and M-IMRT groups was 61 vs. 26 months, respectively (P<0.001). M-IMRT resulted in a significant reduction in median rectal Dmax, rectal V75, rectal V70, rectal V65, bladder Dmax, bladder V75, bladder V70 and bladder V65 (P<0.01 for all). There was no significant difference in rectal V50. The 2-year rate of late grade ≥2 rectal bleeding was 13% with C-IMRT vs. 3% with M-IMRT (P=0.03). The 2-year rate of late grade ≥2 genitourinary toxicity was 11% for C-IMRT vs. 5% for M-IMRT (P=0.21). There were no significant differences in acute toxicity, biochemical control or overall survival. Therefore, compared with C-IMRT, M-IMRT was associated with reduced rectal toxicity without compromising disease control.

Radiation Oncology Physician Practice in the Modern Era: A Statewide Analysis of Medicare Reimbursement.

INTRODUCTION: In recent years, major changes in health care policy have affected oncology practice dramatically. In this context, we examined the effect of practice structure on volume and payments for radiation oncology services using the 2013 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF) for New York State radiation oncologists. METHODS: The Medicare POSPUF data was queried, and individual physicians were classified into freestanding office-based and hospital-based practices. Freestanding practices were further subdivided into urology, hematology-oncology, and other ownership structures. Additional variables analyzed included gender, year of medical school graduation, and Herfindahl-Hirschman Index (HHI). Statistical analyses were performed to assess the impact of the above-mentioned variables on reimbursements. RESULTS: There were 236 New York State radiation oncologists identified in the 2013 Medicare POSPUF dataset, with a total reimbursement of $91,525,855. Among freestanding centers, the mean global Medicare reimbursement was $832,974. Global Medicare reimbursement was $1,328,743 for urology practices, compared to $754,567 for hematology-oncology practices and $691,821 for other ownership structures (p < 0.05). The mean volume of on-treatment visits (OTVs) was 240.5 per year, varying by practice structure. The mean annual OTV volumes for urology practices, hematology-oncology practices, other freestanding practices, and hospital-based programs were 424.6, 311.5, 247.5, and 209.3, respectively. After correcting for gender, physician experience, and HHI, practice structure was predictive of freestanding reimbursement and on treatment visit volume. CONCLUSION: Higher Medicare payment was significantly predicted by the type of practice structure, with urology-based and hematology-oncology practices accounting for the highest total reimbursement and OTV volume.

Effects of combined sunitinib and extracranial stereotactic radiotherapy on bone marrow hematopoiesis.

There is considerable interest in deploying stereotactic body radiotherapy in combination with immune therapy for patients with extracranial oligometastases. In addition to angiogenesis inhibition, sunitinib appears to mediate antitumor immunity through effects on circulating monocytic cells. The current study investigated the effects of combined sunitinib and stereotactic radiotherapy on hematopoiesis. As part of a phase I/II clinical trial utilizing concurrent sunitinib (25-50 mg on days 1-28) and image-guided radiation therapy (40-50 Gy in 10 fractions starting on days 8-19) for patients with metastatic cancer, the complete blood count, platelet count and automatic differential were performed pretreatment and on days 8 and 19. On average, sunitinib monotherapy for 7 days resulted in a 33% decrease in monocytes and an 18% decrease in neutrophils (P<0.01 for all). Compared to sunitinib alone, combined sunitinib and radiation resulted in a further decrease in neutrophils, lymphocytes and platelets (P<0.05). Following sunitinib and radiation treatment, a greater than average decrease in monocytes (≥200/µl) was associated with a significant increase in progression-free and overall survival times. This exploratory study provides further evidence that monocytes represent a potential biomarker in patients with solid tumors treated with sunitinib.

Correction: Clinical Predictors of Survival for Patients with Stage IV Cancer Referred to Radiation Oncology.

[This corrects the article DOI: 10.1371/journal.pone.0124329.].

Esophagus and Contralateral Lung-Sparing IMRT for Locally Advanced Lung Cancer in the Community Hospital Setting.

BACKGROUND: The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. METHODS: We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT). From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity, and overall survival. RESULTS: Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 vs. 60.8 Gy, p = 0.04), patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, esophageal V60, and mean esophagus doses compared to patients treated with standard RT (p ≤ 0.001). Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0 vs. 11%, p < 0.001), acute grade ≥2 weight loss (2 vs. 16%, p = 0.04), and late grade ≥2 pneumonitis (7 vs. 21%, p = 0.02). The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p = 0.015). CONCLUSION: These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose-volume constraints are feasible in the community hospital setting without sacrificing disease control.

Myeloid-Derived Suppressor Cells as an Immune Parameter in Patients with Concurrent Sunitinib and Stereotactic Body Radiotherapy.

PURPOSE: The clinical effects of sunitinib on human myeloid-derived suppressor cell (MDSC) subsets and correlation of the T-cell-mediated immune responses and clinical outcomes in patients with oligometastases treated by stereotactic body radiotherapy (SBRT) have been evaluated. EXPERIMENTAL DESIGN: The numbers of granulocytic and monocytic MDSC subsets, effector T cells, and regulatory T cells in the peripheral blood were evaluated pre- and post-sunitinib treatment and concurrent with SBRT. Correlations between MDSC, Treg, and T-cell responses and clinical outcomes were analyzed. RESULTS: Patients with oligometastases of various cancer types had elevated granulocytic MDSC and certain subsets of monocytic MDSC population. Sunitinib treatment resulted in a significant reduction in monocytic MDSC, phosphorylated STAT3, and arginase levels in monocytic MDSC (CD33(+)CD14(+)CD16(+)), and an increase in T-cell proliferative activity in cancer patients. Interestingly, the effects of sunitinib on reducing the accumulation and immune-suppressive function of MDSC were significantly correlated with Treg reduction, in responders but not in nonresponding patients. SBRT synergized the therapeutic effects of sunitinib, especially as related to decreased numbers of monocytic MDSC, Treg, and B cells, and augmented Tbet expression in primary CD4 and CD8 T cells. These effects were not observed in patients receiving radiation therapy alone. Most interestingly, the responders, defined by sunitinib-mediated reduction in CD33(+)CD11b(+) myeloid cell populations, tend to exhibit improved progression-free survival and cause-specific survival. CONCLUSIONS: Sunitinib treatment increased the efficacy of SBRT in patients with oligometastases by reversing MDSC and Treg-mediated immune suppression and may enhance cancer immune therapy to prevent tumor recurrence post-SBRT.

Clinical Predictors of Survival for Patients with Stage IV Cancer Referred to Radiation Oncology.

BACKGROUND: There is an urgent need for a robust, clinically useful predictive model for survival in a heterogeneous group of patients with metastatic cancer referred to radiation oncology. METHODS: From May 2012 to August 2013, 143 consecutive patients with stage IV cancer were prospectively evaluated by a single radiation oncologist. We retrospectively analyzed the effect of 29 patient, laboratory and tumor-related prognostic factors on overall survival using univariate analysis. Variables that were statistically significant on univariate analysis were entered into a multivariable Cox regression to identify independent predictors of overall survival. RESULTS: The median overall survival was 5.5 months. Four prognostic factors significantly predicted survival on multivariable analysis including ECOG performance status (0-1 vs. 2 vs. 3-4), number of active tumors (1 to 5 vs. ≥ 6), albumin levels (≥ 3.4 vs. 2.4 to 3.3 vs. < 2.4 and primary tumor site (Breast, Kidney or Prostate vs. Other). Risk group stratification was performed by assigning points for adverse prognostic factors resulting in very low, low, intermediate and high risk groups. The median survival was > 31.4 months for very low risk patients compared to 14.5 months for low risk, 4.1 months for intermediate risk and 1.2 months for high risk (p < 0.001). CONCLUSIONS: These data suggest that a model that considers performance status, extent of disease, primary tumor site and serum albumin represents a simple model to accurately predict survival for patients with stage IV cancer who are potential candidates for radiation therapy.