A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible MIBC: the RAD VACCINE MIBC trial.

The utilization of neoadjuvant immune checkpoint inhibitor therapy, specifically anti-PD-1/L1 agents, prior to radical cystectomy is an emerging paradigm in muscle-invasive bladder cancer (MIBC). In situ vaccination represents a strategy to manipulate the tumor in order to augment the immune response toward improved local and distant cancer control. The authors describe the study rationale, design and objectives for RAD VACCINE MIBC, a single-arm, single-institution, phase II trial evaluating the efficacy and safety of combination neoadjuvant sasanlimab (humanized IgG monoclonal antibody that targets PD-1) with stereotactic body radiotherapy as an in situ vaccine in cisplatin-ineligible patients with MIBC. The results from this trial will establish the safety profile of this combination strategy and evaluate pathologic complete response rates.

RAD VACCINE MIBC is a phase II clinical trial that aims to determine the safety and effectiveness of a study drug called sasanlimab (an immune checkpoint inhibitor), combined with radiation therapy (stereotactic body radiation therapy) prior to surgery to remove the bladder (known as radical cystectomy [RC]) in muscle-invasive bladder cancer patients. For this type of cancer, patients typically receive chemotherapy followed by RC as the standard of care. However, many patients who have pre-existing medical conditions such as poor kidney function are unable to receive chemotherapy. These patients undergo RC alone at the risk of less optimal cancer control. Bladder cancer is known to inhibit the immune cells (T cells) from attacking it, which is an important way in which the body controls cancer cells. Sasanlimab allows T cells that are specific to the cancer to potentially reactivate. Ongoing studies have shown that drugs similar to sasanlimab can be used to achieve improvement in cancer control in the bladder (as measured by shrinking the cancer or eradicating it) before surgery. The authors are studying the use of the study drug with the addition of stereotactic body radiotherapy (SBRT) as a combined therapy. The role of SBRT as a combined therapy to immune checkpoint inhibition has been well studied to help improve the process of how immune cells recognize cancer cells. By giving both the study drug and SBRT together before RC, the authors aim to demonstrate the safety of this technique and its effectiveness in eradicating all cancer in the bladder. Clinical Trial Registration: NCT05241340 (ClinicalTrials.gov).

The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast.

BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER 2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.

Approach to radiation therapy in the Jehovah's Witness patient: An overview.

Jehovah's Witnesses are well-known in the medical community for their inability to accept blood products. Novel methods of treatment are often needed to avoid anemia and hematologic toxicity as inability to receive blood products may increase the risk of treatment related complications. We provide an overview of radiation treatment for Jehovah's Witness patients with an emphasis on bone marrow sparing strategies with intensity modulated radiation therapy (IMRT) to minimize hematologic toxicity.

The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma.

BACKGROUND: Pleural mesothelioma is a rare but aggressive form of cancer. Local recurrence represents the majority of treatment failures and overall survival (OS) outcomes remain dismal. Adding locoregional treatment with radiotherapy after surgical resection has been considered but its role remains uncertain. OBJECTIVE: The purpose of this study was to evaluate the outcomes of adjuvant radiation therapy (RT) for patients with malignant pleural mesothelioma. METHODS: The National Cancer Data Base (NCDB) was queried (2004-2013) for patients with malignant mesothelioma. Patients were divided into three groups: observation, surgery alone, and surgery followed by adjuvant RT. Statistics included Fisher's exact or Chi square tests to analyze categorical proportions between groups, Kaplan-Meier analysis to evaluate OS, and Cox proportional hazards modeling to determine variables associated with OS. Propensity matching was performed to make comparisons between homogenous groups. RESULTS: Overall, the surgery plus radiotherapy group had a higher median survival (21.4 months) compared with surgery alone (16.59 months) [p < 0.001]. RT was more likely to be delivered after extrapleural pneumonectomy than with lung-sparing surgical approaches. On multivariable analysis, receipt of surgery plus radiotherapy, chemotherapy administration, and higher socioeconomic status were associated with improved OS (p < 0.0001). After propensity matching, receipt of surgery plus radiotherapy and chemotherapy administration were still associated with improved OS (p < 0.05). CONCLUSIONS: In the treatment of malignant pleural mesothelioma, adjuvant radiotherapy after surgical intervention was associated with improved OS. This study is the largest study of adjuvant radiotherapy to date, and our findings highlight the need for additional prospective data.

Socioeconomic Factors Associated with Lack of Treatment in Early Stage Non-Small Cell Lung Cancer.

With modern radiotherapy, stage I non-small cell lung cancer (S1NSCLC) cure is extended to nonsurgical candidates. Despite this, some S1NSCLC remains untreated. We aim to identify factors associated with no treatment. 62,213 S1NSCLC cases were identified (SEER: 2004-2012). Demographics were compared using Chi-squared. Multivariate analysis was performed using COX proportional HR. 11.9% of the 7373 patients lacked treatment. No insurance, Medicaid-dependence, unmarried status, advancing age, lower income, African American and Asian/Pacific Islander race, and male sex are associated with no treatment (p < .0001). No treatment portends a worse cancer-specific survival (21% vs 66% at 5Y, p < .0001) and OS (10% vs 50% at 5Y, p < .0001).

The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)-positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow-up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2- disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR-HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African-American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.

Neuronal Trans-Differentiation in Prostate Cancer Cells.

BACKGROUND: Neuroendocrine (NE) differentiation in prostate cancer (PCa) is an aggressive phenotype associated with therapy resistance. The complete phenotype of these cells is poorly understood. Clinical classification is based predominantly on the expression of standard NE markers. METHODS: We analyzed the phenotype of NE carcinoma of the prostate utilizing in vitro methods, in silico, and immunohistochemical analyses of human disease. RESULTS: LNCaP cells, subjected to a variety of stressors (0.1% [v/v] fetal bovine serum, cyclic AMP) induced a reproducible phenotype consistent with neuronal trans-differentiation. Cells developed long cytoplasmic processes resembling neurons. As expected, serum deprived cells had decreased expression in androgen receptor and prostate specific antigen. A significant increase in neuronal markers also was observed. Gene array analysis demonstrated that LNCaP cells subjected to low serum or cAMP showed statistically significant manifestation of a human brain gene expression signature. In an in silico experiment using human data, we identified that only hormone resistant metastatic prostate cancer showed enrichment of the "brain profile." Gene ontology analysis demonstrated categories involved in neuronal differentiation. Three neuronal markers were validated in a large human tissue cohort. CONCLUSION: This study proposes that the later stages of PCa evolution involves neuronal trans-differentiation, which would enable PCa cells to acquire independence from the neural axis, critical in primary tumors. Prostate 76:1312-1325, 2016. © 2016 Wiley Periodicals, Inc.

A Phase 2 Study of In Situ Oncolytic Virus Therapy and Stereotactic Body Radiation Therapy Followed by Pembrolizumab in Metastatic Non-Small Cell Lung Cancer.

PURPOSE: A phase 2 study of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single pembrolizumab with ADV/HSV-tk plus valacyclovir gene therapy and SBRT in mNSCLC. METHODS AND MATERIALS: STOMP is a single-arm, open-label phase 2 study. Patients with mNSCLC received intratumoral injections of ADV/HSV-tk (5 × 1011 vp) and SBRT (30 Gy in 5 fractions) followed by pembrolizumab 200 mg IV every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR) (complete response [CR] and partial response [PR]). Secondary endpoints included clinical benefit rate (CBR) (CR, PR and stable disease [SD]), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 28 patients were enrolled, of whom 27 were evaluated for response. The ORR was 33.3%, including 2 CR (7.4%) and 7 PR (25.9%). CBR was 70.4%. Six of eight (75.0%) patients who were immune checkpoint inhibitor (ICI) refractory derived clinical benefits. Responders had durable responses with median PFS, and OS not reached. The entire cohort had a median PFS of 7.4 months (95% CI, 5.1-9.6 months), and median OS of 18.1 months (95% CI, 15.4-20.9 months). The combination was well tolerated, with grade 3 or higher toxicity in 6 (21.4%) patients. CONCLUSIONS: The dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy-sparing strategy to enhance the antitumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC.

Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.

INTRODUCTION: Elective pelvic nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT ) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiation (WP-CCR) compared to bladder-only (BO )-CCR has not been demonstrated. Using real-world data from the National Cancer Database (NCDB ), we sought to compare the overall survival (OS ) between BO-CCR and WP-CCR for MIBC. METHODS: Using the 2020 NCDB Participant User File, we identified cases of MIBC diagnosed between 2017 and 2019. We selected patients with clinical T2-T4aN0M0 disease receiving CCR as first-line treatment. CCR was defined as transurethral resection of bladder tumor followed by ≥40 Gy radiation to the bladder with concurrent single- or multiple-agent chemotherapy. Based on elective nodal irradiation status, patients were stratified as having received BO-CCR vs. WP-CCR. OS analysis was performed using summary three-month conditional landmark, inverse probability treatment weighting (IPTW)-adjusted Kaplan-Meier estimates, and Cox regression. RESULTS: A total of 604 patients receiving CCR for MIBC were identified: 367 (60.8%) BO-CCR and 237 (39.2%) WP-CCR. Before IPTW, the groups were imbalanced in terms of baseline characteristics. The median followup of the weighted population was 42.3 months (interquartile range 18.1-49.1 months). In IPTW-adjusted Cox proportional hazards regression analysis, WP-CCR was associated with a significant OS benefit compared to BO-CCR (adjusted hazard ratio 0.72, 95% confidence interval 0.54-0.96, p=0.026). CONCLUSIONS: In the setting of CCR for N0 MIBC, this retrospective NCDB analysis revealed that WP-CCR was associated with a benefit in OS compared to BO-CCR.

Therapeutic challenges in treating patients with fragile X syndrome and neoplasia.

The administration of cytotoxic therapy to patients with fragile X syndrome (FXS) presents several unique therapeutic challenges. The existence of fragile sites poses a theoretical risk of tumorigenesis and potentially increased treatment associated toxicity, however, controversy exists. We review the 42 previously reported cases of neoplasia in patients with FXS and report two novel neoplasms in patients treated with radiation therapy or combined chemoradiation. Our experience suggests that radiation therapy can be delivered safely in these patients without an expectation for increased acute/sub-acute normal tissue toxicity; however, treatment requires specialized facilities with the resources to deliver this care safely.

Focal versus whole gland salvage brachytherapy for recurrent prostate cancer in the prostate specific membrane antigen PET era: a narrative review.

BACKGROUND AND OBJECTIVE: Prostate cancer is the second most common cause of cancer in men worldwide. A significant proportion of patients will develop biochemical failure after definitive radiotherapy and an increasing number of local failures are now identifiable with prostate specific membrane antigen (PSMA) positron emission tomography and computerized tomography (PET/CT). Brachytherapy (BT) represents an excellent option for definitive local salvage treatment. Consensus guidelines for the delivery of salvage BT are heterogenous and limited. Herein, we report the results from a narrative review analyzing whole gland and partial gland BT salvage to help guide treatment recommendations. METHODS: The PubMed and MEDLINE databases were searched in October 2022 to identify studies analyzing BT salvage in patients with recurrent prostate cancer after definitive external beam radiation therapy (EBRT). 503 initial studies met search criteria. After title and abstract screening, 25 studies met inclusion criteria and full-text review was performed. Twenty studies were included for analysis. Reports included whole gland (n=13) and partial gland or focal (n=7) salvage BT. KEY CONTENT AND FINDINGS: The median 5-year biochemical failure free survival (BFFS) for men receiving whole gland BT salvage was 52%, which is comparable to 5-year recurrence-free survival (RFS) rates for other salvage treatment modalities (radical prostatectomy (RP) 54%, high-intensity focused ultrasound (HIFU) 53%, cryotherapy 50%). However, the median rate of severe genitourinary (GU) toxicity was lower (12%) compared to published rates for other treatment modalities (RP 21%, HIFU 23%, and cryotherapy 15%). Furthermore, patients receiving partial gland salvage BT had even lower median rates of grade 3 or higher GU toxicity (4% vs. 12%) and gastrointestinal (GI) toxicity (0% vs. 3%), with 3-year BFFS of 58%. Only two studies directly comparing BT whole versus partial gland salvage were identified with comprehensive literature search and neither provided specific comparison regarding prescription dose or dose constraints. CONCLUSIONS: This narrative review identified only two studies that directly compared whole versus partial gland BT salvage treatment. Neither report provided a specific comparison of recommendations for dosimetric technique or normal structure dose constraints. Therefore, this review highlights a significant gap in the existing literature and provides an important framework to guide radiation treatment (RT) recommendations for both whole gland and partial gland salvage BT in patients with recurrent prostate cancer.

Radiation Pneumonitis, Really? A Case of Pulmonary Toxicity from CDK4/6 Inhibitor.

BACKGROUND/AIM: Radiation pneumonitis is a known complication of radiotherapy. It is also a rare complication of CDK4/6 inhibitors, and it can be difficult to differentiate the two. This is a report of a case of pulmonary toxicity from a CDK4/6 inhibitor, which was initially ascribed to radiation pneumonitis. CASE REPORT: A 77-year-old female was diagnosed with pneumonitis after receiving radiation to the thoracic spine. She had also been treated with abemaciclib. Upon review, the patient's lung mean dose was 11.54 Gy with a V20 of 17.02%, and the area of pneumonitis was largely outside of the treatment field. Abemaciclib was ceased. The patient was started on supportive oxygen as well as steroids. She no longer required oxygen and she was discharged from the hospital. Radiation pneumonitis is largely correlated with the volume of lung radiated and dose of radiation to the lung. CDK4/6 inhibitor pulmonary toxicity, while rare, is possible and will likely become more frequent with increasing use of these agents. CONCLUSION: Patients receiving CDK4/6 inhibitors are at an increased risk for pneumonitis. It can be confused with radiation pneumonitis and must be included in the differential diagnosis.

Leptomeningeal metastasis from neuroendocrine carcinoma of the cervix: illustrative case.

BACKGROUND: Leptomeningeal carcinomatosis is a rare feature of metastasis that is characterized by thickening and increased contrast enhancement throughout the meninges of the central nervous system (CNS). Leptomeningeal disease (LMD) can occur as spread from primary CNS tumors or as a manifestation of metastasis to the CNS from primary tumor sites outside the CNS. Leptomeningeal disease is, however, rare in cervical cancer, in which metastasis occurs typically from local invasion. OBSERVATIONS: The authors discuss the case of CNS metastasis with LMD from the rare neuroendocrine carcinoma of the cervix (NECC). Cervical cancer infrequently metastasizes to the CNS, but NECC is an aggressive variant with greater metastatic potential. Many of these patients will have previously received pelvic radiation, limiting their candidacy for craniospinal radiation for LMD treatment due to field overlap. This illustrative case documents the first known case of NECC CNS metastasis accompanied by LMD treated with intrathecal chemotherapy. LESSONS: Reported is the first known case of NECC with CNS metastasis accompanied by LMD. The authors highlight the potentially critical role of intrathecal chemotherapy, in addition to radiotherapy, in treating leptomeningeal metastasis from cervical cancer.

Hepatocellular Carcinoma Recurrence as Isolated Adrenal Metastasis.

Hepatocellular carcinoma is the sixth most common cancer in the Western world. The most frequent sites of metastasis are lungs, lymph nodes, and bones. Risk factors for extrahepatic metastasis are advanced intrahepatic lesions, vascular invasion, elevated tumor markers, and viral hepatitis. Isolated metachronous adrenal metastasis occurring after liver transplantation is exceedingly rare.

A feasibility study of utilizing a cadaveric training model for novel robotic bladder cancer brachytherapy techniques.

PURPOSE: The current standard of care for muscle-invasive bladder cancer is neoadjuvant chemotherapy followed by radical cystectomy with lymph node dissection. Although this treatment provides therapeutic benefit, it is associated with notable morbidity. Bladder sparing techniques, such as concurrent chemo-radiation, are less invasive and prioritize organ preservation in individuals with invasive bladder cancer and offer comparable disease control. High-dose-rate brachytherapy is an emerging paradigm in the management of muscle-invasive bladder cancer. During high-dose-rate brachytherapy, radioactive sources are introduced to the area of the primary tumor through specialized catheters. The specific placement of brachytherapy catheters results in heightened effectiveness of the radiation treatment with less radiation damage to surrounding structures. For bladder-sparing therapies such as brachytherapy to rival radical cystectomy, these techniques need to be refined further by radiation oncologists. PROCEDURE: One such modality for developing and practicing these techniques is the use of cadaveric models in innovation-focused clinical training facilities, which provide a simulated sterile surgical environment without the concern for extending intraoperative time. FINDINGS AND CONCLUSIONS: The objective of this technical note is to demonstrate how clinical training facilities such as the Houston Methodist Institute for Technology, Innovation & Education are ideal for the development, testing, and training of novel brachytherapy techniques using cadaveric models. By utilizing a network of similarly innovative training centers, research and development of brachytherapy techniques can be expedited, and novel bladder-sparing treatment methods can be implemented as the standard of care for bladder cancer.

Microfluidic coaxial 3D bioprinting of cell-laden microfibers and microtubes for salivary gland tissue engineering.

Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC). Currently, only palliative treatments exist for xerostomia, and many patients endure deteriorated oral health and poor quality of life. Tissue engineering could offer a permanent solution for SG replacement by isolating healthy SG tissues prior to RT, expanding its cells in vitro, and recreating a functional salivary neogland for implantation post-RT. 3D bioprinting methods potentiate spatial cell deposition into defined hydrogel-based architectures, mimicking the thin epithelia developed during the complex branching morphogenesis of SG. By leveraging a microfluidics-based bioprinter with coaxial polymer and crosslinker streams, we fabricated thin, biocompatible, and reproducible hydrogel features that recapitulate the thin epithelia characteristics of SG. This flexible platform enabled two modes of printing: we produced solid hydrogel fibers, with diameters <100 µm, that could be rastered to create larger mm-scale structures. By a second method, we generated hollow tubes with wall thicknesses ranging 45-80 µm, total tube diameters spanning 0.6-2.2 mm, and confirmed tube patency. In both cases, SG cells could be printed within the thin hydrogel features, with preserved phenotype and high viability, even at high density (5.0 × 106 cells/mL). Our work demonstrates hydrogel feature control across multiple length scales, and a new paradigm for addressing SG restoration by creating microscale tissue engineered components.

Role of 21-Gene Recurrence Score in Predicting Prognostic Benefit of Radiation Therapy After Breast-Conserving Surgery for T1N0 Breast Cancer.

PURPOSE: The 21-gene RT-PCR recurrence score (RS) is performed in patients with hormone receptor-positive (ER+, PR+), human epidermal growth factor receptor 2 (HER2)-negative, N0 breast cancer to determine which patients will likely benefit from chemotherapy after breast-conserving surgery (BCS). The purpose of this study was to evaluate whether the RS can predict for patients likely to benefit from radiation therapy (RT) after BCS. METHODS AND MATERIALS: The National Cancer Database was queried (2004-2017) for female patients with pT1N0 ER+ PR+ HER2-negative breast cancer treated with BCS who had an available RS. Patients were stratified based on their RS (low risk [LR], 1-10; intermediate risk [IR], 11-25; high risk [HR], 26-100). For each RS cohort, propensity score matching was conducted to create 1:1 matched cohorts of patients who received RT and patients who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable and multivariable (MVA) Cox proportional hazard analysis identified clinical and treatment factors prognostic for OS. RESULTS: A total of 79,040 patients met the selection criteria: 18,823 in the LR cohort, 52,341 in the IR cohort, and 7876 in the HR cohort. A total of 92% of patients received RT: 91% in the LR cohort, 93% in the IR cohort, and 92% in the HR cohort. After propensity score matching, the 5-year OS in the LR cohort was 95% for those who received RT and 93% for those who did not (P = .184). In the IR cohort, the 5-year OS was 95% for those who received RT and 93% for those who did not (P = .001). In the HR cohort, the 5-year OS was 95% for those who received RT and 84% for those who did not (P < .001). MVA demonstrated that RT was a positive prognostic factor for OS in both the IR cohort (P = .001) and HR cohort (P < .001). On MVA in the LR cohort, RT (P = .186) was not predictive of improved OS. CONCLUSIONS: An OS benefit was observed with the use of RT in patients with IR or HR RS but not in patients with LR RS. Future prospective evaluation is warranted.

Prognostic impact of biologically equivalent dose in stereotactic body radiotherapy for renal cancer.

Purpose /Objectives Materials/Methods: The National Cancer Database (NCDB) was queried (2004-2017) for patients with RCC who did not have surgical resection but received definitive SBRT. Kaplan-Meier analysis with log-rank test was used to evaluate overall survival (OS). Univariable (UVA) and multivariable (MVA) analysis were conducted using cox proportional hazard models to determine prognostic factors for OS. Results: A total of 344 patients with median age 77 (IQR 70-85) were included in this study. Median BED3 was 180 Gy (IQR 126.03-233.97). Median OS was 90 months in the highest quartile compared to 36-52 months in the lower three quartiles (p < 0.01). On UVA, the highest BED3 quartile was a positive prognostic factor (HR 0.67, p < 0.01 CI 0.51-0.91) while age, tumor size, T-stage, metastasis, renal pelvis location, and transitional cell histology were negative factors. On MVA, the highest BED3 quartile was remained significant (HR 0.69, p = 0.02; CI 0.49-0.95) as a positive factor, while age, metastasis were negative factors. Conclusion: Higher BED may be associated with improved OS. Prospective investigation is needed to clearly define optimal BED for SBRT used to treat RCC.

21-Gene recurrence score predictive for prognostic benefit of radiotherapy in patients age ≥ 70 with T1N0 ER/PR + HER2- breast cancer treated with breast conserving surgery and endocrine therapy.

PURPOSE: Based on the results of the Cancer and Leukemia Group B (CALGB) 9343 trial, patients age ≥70 with T1N0 hormone receptor positive (ER/PR+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). Because the CALGB 9343 trial did not stratify based on recurrence score (RS) test (Oncotype Dx), we conducted the present retrospective study to determine whether RS is predictive of who may benefit from RT following BCS in this cohort. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried (2004-2017) for patients age ≥ 70 with pT1N0 ER+/PR + HER2- breast cancer treated with BCS and ET. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). Propensity score matching (PSM) created 1:1 matched cohorts of patients who received radiotherapy and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS. RESULTS: A total of 11,891 patients met the selection criteria: 3364 in the LR cohort, 7305 in the IR cohort, and 1222 in the HR cohort. A total of 79 % received RT: 77 % in the LR cohort, 79 % in the IR cohort, and 85 % in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, the 5-year OS in the LR cohort was 91 % for those who received RT and 89 % for those who did not (p = 0.605). In the IRHR cohort, the 5-year OS was 91 % for those who received RT and 87 % for those who did not (p = 0.003). On MVA in the LR cohort, RT (p = 0.727) was not predictive of improved OS. On MVA in the IRHR cohort, RT (p = 0.010) was a positive prognostic factor for OS. CONCLUSION: In this older cohort of patients, there is an OS benefit with the use of RT in patients with IRHR RS but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.