Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation.

BACKGROUND: As systemic therapy has improved for locally advanced pancreatic cancer (LAPC), efforts to improve local control with optimal radiotherapy may be critical. Although conventionally fractionated radiation therapy (CFRT) has more recently shown a limited role in LAPC, stereotactic body radiation therapy (SBRT) is an emerging approach with promising results. With no studies to date comparing SBRT with CFRT for LAPC, this study used the National Cancer Data Base (NCDB) to evaluate these 2 modalities. METHODS: With the NCDB, patients with American Joint Committee on Cancer cT2-4/N0-1/M0 adenocarcinoma of the pancreas diagnosed from 2004 to 2013 were analyzed. Radiation therapy delivered at ≤2 Gy was deemed CFRT, and radiation therapy delivered at ≥4 Gy per fraction was considered SBRT. Kaplan-Meier analysis, log-rank testing, and multivariate Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching was used. RESULTS: Among 8450 patients, 7819 (92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. Receipt of SBRT was associated with superior OS in the multivariate analysis (hazard ratio, 0.84; 95% confidence interval, 0.75-0.93; P < .001). With propensity score matching, 988 patients in all were matched, with 494 patients in each cohort. Within the propensity-matched cohorts, the median OS (13.9 vs 11.6 months) and the 2-year OS rate (21.7% vs 16.5%) were significantly higher with SBRT versus CFRT (P = .0014). CONCLUSIONS: In this retrospective review using a large national database, SBRT was associated with superior OS in comparison with CFRT for LAPC, and these findings remained significant in a propensity-matched analysis. Further prospective studies investigating these hypothesis-generating results are warranted. Cancer 2017;123:3486-93. © 2017 American Cancer Society.

Neuromuscular electrical stimulation improves radiation-induced fibrosis through Tgf-Β1/MyoD homeostasis in head and neck cancer.

OBJECTIVES: The purpose of this study was to analyze TGF-ß1 and MyoD expression in cervical muscles during radiation therapy (RT) and their role in inducing muscle fibrosis in head and neck cancer (HNC) patients. We also studied the effect of combined traditional swallow therapy (TST) and neuromuscular electrical stimulation (NMES) therapy on TGF-ß1/MyoD homeostasis in patients undergoing post-operative RT for HNC. STUDY DESIGN: Case-control study. METHODS: Thirty patients, 10 with benign thyroid lesions and non-radiated muscle (control), and 20 with advanced-stage HNC receiving primary resection and post-operative radiation (study group) were enrolled. Patients in the study group were randomly assigned to receive post-operative RT alone (Group I) or post-operative RT with TST/NMES therapy (Group II). Intraoperative biopsies were obtained in all 30 patients. In the study groups, biopsies were repeated 4 weeks after completion of RT. TGF-ß1 and MyoD expression were evaluated by immunohistochemistry and Western Blot. RESULTS: The control group demonstrated low expression of TGF-ß1 and high expression of MyoD. Following RT, patients in study Group I had high expression of TGF-ß1 and low levels of MyoD. Group II patients demonstrated TGF-ß1 levels more consistent with that of non-irradiated tissue. CONCLUSION: The molecular pathogenesis of RT-induced muscle fibrosis involves the TGF-ß1 pathway and its repression of MyoD expression. Our results suggest a correlation between TST/NMES combined therapy and the restoration of TGF-ß1/MyoD homeostasis in cervical muscles. TST/NMES is a plausible prophylaxis and/or treatment for RT-induced muscle fibrosis and dysphagia. J. Surg. Oncol. 2016;114:27-31. © 2016 Wiley Periodicals, Inc.

Prospective surveillance of patients after palliative radiation for painful bone metastases: a feasibility study.

BACKGROUND: Bone metastasis is the most common cause of cancer-related pain. Radiation therapy (RT) can provide successful palliation but there is currently no consensus for surveillance after palliative radiation. This study aimed to assess the feasibility of surveillance after RT for painful bone metastases. METHODS: The study took place in an academic cancer center. Patient feasibility measures included % of calls answered, ease of recruitment and study retention. Clinician measures included % of calls made within 3 days, call time and qualitative feedback. Patients were identified with a painful bone metastasis treated with RT. The bone metastasis had a worst pain score of at least 4 (0-10 scale), with pain localized to a radiographically confirmed lesion. Patients were called at weeks 1, 4 and 8 following RT. Pain response and opioid use were assessed. Quality of life was assessed using a validated questionnaire. Descriptive statistics were used to assess if these metrics were met for patients and clinicians over 8 weeks post-RT. RESULTS: Twenty patients were consented: 14 participants completed treatment and were not hospitalized or deceased prior to week 1. The patients were 50% male and 50% female. Recruitment was completed quickly, with no patients withdrawing. Response rate was week 1: 85% week 4: 83% and week 8: 83%. Six patients were referred back to their provider for pain management. Calls were made to patients within 3 days a median of 63% of the time (range, 40-82%), with a median call time of 16 (range, 8-42) minutes. Call lengths were longer for patients who required interpretation. Nurse feedback highlighted length of call and nursing time available as limitations. CONCLUSIONS: All patient feasibility measures were met. Six patients required further pain management, highlighting a need for improved follow up post-RT for bone metastases. Staffing challenges for this intervention must be overcome.

Prognostic nomogram of overall survival for radiation therapy in hepatocellular carcinoma: a population study based on the SEER database and an external cohort.

Purpose: Radiotherapy (RT) plays an important role in the treatment of hepatocellular carcinoma (HCC). To screen patients who benefit most from RT, a nomogram for survival prediction of RT based on a large sample of patients with HCC was created and validated. Methods: A total of 2,252 cases collected from the Surveillance, Epidemiology, and End Results (SEER) database were separated into a training or an internal validation cohort in a 7:3 ratio (n = 1,565:650). An external validation cohort of cases from our institute was obtained (n = 403). LASSO regression and Cox analyses were adopted to develop a nomogram for survival prediction. The decision curve analysis (DCA), calibration curve, and time-dependent receiver operating characteristic curves (TROCs) demonstrated the reliability of the predictive model. Results: For patients with HCC who received RT, the analyses revealed that the independent survival prediction factors were T stage {T2 vs. T1, hazard ratio (HR) =1.452 [95% CI, 1.195-1.765], p < 0.001; T3 vs. T1, HR = 1.469 [95% CI, 1.168-1.846], p < 0.001; T4 vs. T1, HR = 1.291 [95% CI, 0.951-1.754], p = 0.101}, N stage (HR = 1.555 [95% CI, 1.338-1.805], p < 0.001), M stage (HR = 3.007 [95% CI, 2.645-3.418], p < 0.001), max tumor size (>2 and ≤5 vs. ≤2 cm, HR = 1.273 [95% CI, 0.992-1.633], p = 0.057; >5 and ≤10 vs. ≤2 cm, HR = 1.625 [95% CI, 1.246-2.118], p < 0.001; >10 vs. ≤2 cm, HR = 1.784 [95% CI, 1.335-2.385], p < 0.001), major vascular invasion (MVI) (HR = 1.454 [95% CI, 1.028-2.057], p = 0.034), alpha fetoprotein (AFP) (HR = 1.573 [95% CI, 1.315-1.882], p < 0.001), and chemotherapy (HR = 0.511 [95% CI, 0.454-0.576], p < 0.001). A nomogram constructed with these prognostic factors demonstrated outstanding predictive accuracy. The area under the curve (AUC) in the training cohort for predicting overall survival (OS) at 6, 12, 18, and 24 months was 0.824 (95% CI, 0.803-0.846), 0.824 (95% CI, 0.802-0.845), 0.816 (95% CI, 0.792-0.840), and 0.820 (95% CI, 0.794-0.846), respectively. The AUCs were similar in the other two cohorts. The DCA and calibration curve demonstrated the reliability of the predictive model. Conclusion: For patients who have been treated with RT, a nomogram constructed with T stage, N stage, M stage, tumor size, MVI, AFP, and chemotherapy has good survival prediction ability.

Re-treatment of bone metastases for pain control: 2023 ASTRO education panel.

Bone metastases are a common and debilitating consequence of advanced cancer, often necessitating palliative radiation therapy (RT) for pain relief. Reirradiation (reRT) of bone metastases is often considered after lack of pain relief following an initial course of RT, after a partial but unsatisfying pain response to an initial course of radiotherapy, or after pain recurrence following a complete or partial pain response to an initial course of RT. The NCIC CTG SC.20 trial, a landmark multicenter, randomized, non-blinded, controlled non-inferiority trial, addressed the critical question of optimal dose fractionation for reRT in this patient population. This trial compared the efficacy and toxicity of a single 8 Gy fraction to multiple fractions totaling 20 Gy in 850 patients with painful bone metastases requiring reRT. The primary endpoint was overall pain response at 2 months, with secondary endpoints of quality of life (QoL) measures, functional interference, and toxicity profiles assessed using patient-reported questionnaires and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. The intention-to-treat analysis revealed no significant difference in pain response between the two arms, meeting the pre-specified non-inferiority criteria. The per-protocol analysis suggested a potential benefit for a subset of patients receiving multiple fractions, although this was not statistically robust. Acute toxicities were more prevalent in the multiple fractions arm, with implications for patient comfort and healthcare utilization. Importantly, responders to reRT reported significant improvements in functional interference and QoL. The trial's findings support the use of a patient-centric approach to palliative RT, highlighting the viability of a single 8 Gy fraction as a less toxic and more convenient treatment option, albeit with consideration for individual patient circumstances. These results have significant implications for clinical practice, potentially reducing healthcare burdens while optimizing patient convenience during palliative care for painful bone metastases.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020].

Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

Identifying patients suitable for targeted adjuvant therapy: advances in the field of developing biomarkers for tumor recurrence following irradiation.

Introduction: Radiation therapy (RT) is commonly used to treat cancer in conjunction with chemotherapy, immunotherapy, and targeted therapies. Despite the effectiveness of RT, tumor recurrence due to treatment resistance still lead to treatment failure. RT-specific biomarkers are currently lacking and remain challenging to investigate with existing data since, for many common malignancies, standard of care (SOC) paradigms involve the administration of RT in conjunction with other agents. Areas Covered: Established clinically relevant biomarkers are used in surveillance, as prognostic indicators, and sometimes for treatment planning; however, the inability to intercept early recurrence or predict upfront resistance to treatment remains a significant challenge that limits the selection of patients for adjuvant therapy. We discuss attempts at intercepting early failure. We examine biomarkers that have made it into the clinic where they are used for treatment monitoring and management alteration, and novel biomarkers that lead the field with targeted adjuvant therapy seeking to harness these. Expert Opinion: Given the growth of data correlating interventions with omic analysis toward identifying biomarkers of radiation resistance, more robust markers of recurrence that link to biology will increasingly be leveraged toward targeted adjuvant therapy to make a successful transition to the clinic in the coming years.

Risk prediction of second primary malignancies after gynecological malignant neoplasms resection with and without radiation therapy: a population-based surveillance, epidemiology, and end results (SEER) analysis.

PURPOSE: The association between post-resection radiotherapy for primary gynecological malignant neoplasms (GMNs) and the development of secondary primary malignancies (SPMs) remains a subject of debate. This study represents the first population-based analysis employing a multivariate competitive risk model to assess risk factors for this relationship and to develop a comprehensive competing-risk nomogram for quantitatively predicting SPM probabilities. MATERIALS AND METHODS: In our study, data on patients with primary GMNs were retrospectively collected from the Epidemiology, Surveillance and End Results (SEER) database from 1973 to 2015. The incidence of secondary malignant tumors diagnosed at least six months after GMN diagnosis was compared to determine potential risk factors for SPMs in GMN patients using the Fine and Gray proportional sub-distribution hazard model. A competing-risk nomogram was constructed to quantify SPM probabilities. RESULTS: A total of 109,537 patients with GMNs were included in the study, with 76,675 and 32,862 GMN patients in the training and verification sets, respectively. The competing-risk model analysis identified age, primary tumor location, tumor grade, disease stage, chemotherapy, and radiation as risk factors for SPMs in GMN patients. Calibration curves and ROC curves in both training and verification cohorts demonstrated the predictive accuracy of the established nomogram, which exhibited a good ability to predict SPM occurrence. CONCLUSIONS: This study presents the nomogram developed for quantitatively predicting SPM probabilities in GMN patients for the first time. The constructed nomogram can assist clinicians in designing personalized treatment strategies and facilitate clinical decision-making processes.

Proteomic profiling of metabolic proteins as potential biomarkers of radioresponsiveness for colorectal cancer.

Surgery, radiation therapy (RT), and chemotherapy are commonly used treatment modalities for CRC management. The locally advanced CRC is managed with preoperative RT or in combination of chemoradiotherapy whereas palliative RT is recommended for metastatic CRC patients to enhance overall survival and reduce distressing symptoms. There are many biomarkers established based on tumour staging, grading and molecular characteristics of patients (e.g., mutation, DNA methylation, and gene expression profiling). Interestingly, none of these markers are adequately validated for RT scheme. In order to establish the radioresponsive biomarker in CRC, we established a mouse xenograft tumour model and applied radiation to the tumours. We identified 9 metabolic proteins, namely PGK1, PGAM1, ENO1, PKM, TKT, GLUD1, LDHA, GAPDH, and MDH2, which are differentially expressed in tumours with different radioresponsiveness. Furthermore, we validated their expression in tumours from the unirradiated, poorly responded and highly responded tumour groups. In addition, we analysed their expressions in clinical samples from the public database. Extensive literature studies shown that these metabolic proteins are associated with key biochemical pathways including, glycolysis, ammonia detoxification, carcinogenesis, and drug responses. Further studies are needed to translate our findings into clinical use. SIGNIFICANCE: With the increasing incidence of colorectal cancer (CRC) globally, it is crucial to establish strategic treatment protocol by personalizing cancer treatment. Despite the well-established treatment protocols for CRC in the past decades, the mortality remains high. There is a trend of applying personalized treatment to improve patient survival. It has been reported that biomarkers may be used to predict treatment outcomes or to adjust individual treatment protocols. This project aims to identify specific metabolic proteins as biomarkers for CRC radioresponsiveness. Using bioinformatical analysis, we have identified 9 metabolic proteins which could be used as potential biomarkers for radiation therapy in CRC tumours.

Oligoprogression in non-small cell lung cancer: a narrative review.

Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers and is the most common non-cutaneous cancer world-wide. In NSCLC, oligometastatic and oligoprogressive disease (OPD) have been recognized as separate entities within the realm of metastatic disease and are emerging concepts in the context of targeted systemic therapies. Our objectives are to discuss the current literature regarding the evolving definitions of OPD in the context of oligometastatic disease (OMD) for NSCLC. Further, to discuss current and future clinical trials that have shaped our local approach with stereotactic body radiation therapy (SBRT)/stereotactic ablative radiotherapy (SABR). Methods: Literature on OPD in NSCLC and local ablative therapy (LAT) including SBRT/SABR and stereotactic radiosurgery (SRS) was reviewed. Key Content and Findings: Oligoprogression is defined as limited (usually 3-5) metastatic areas progressing while on/off systemic therapy in the background of oligometastatic or polymetastatic disease. Prognosis in OPD with treatment (such as LAT and systemic therapy) may be more favorable. Outcomes for patients progressing on tyrosine kinase inhibitors (TKIs) with molecular mutations [such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)] who receive LAT are promising. Conclusions: Patients presenting with NSCLC metastasis with progression at a limited number of sites on/off a given line of systemic therapy may have favorable outcomes with aggressive LAT, which includes SBRT/SABR/SRS. Further studies need to be completed to further optimize treatment recommendations.

Radiation therapy for pelvic recurrent colorectal or gynecological cancer: is whole pelvic irradiation necessary?

BACKGROUND: Preoperative whole pelvic radiation therapy (RT) is used commonly for rectal cancer and is the standard field postoperatively in gynecological cancer. However, the ideal field (local vs. whole pelvis) has not been determined for local recurrence of these cancers. METHODS: We retrospectively reviewed the data for 52 patients who developed local tumor recurrence of rectal or gynecological cancer treated from 2013 to 2021. The initial treatment for all patients was total excision of the primary tumors without radiation therapy. Radiation therapy targets were surgical stumps, perianastomosis sites, and pelvic lymph nodes, classified according to the pelvic nodal volume atlas for radiation therapy. Patients were divided into the local recurrent tumor only radiation therapy group and the whole pelvis radiation therapy group. Whole pelvis radiation therapy included the common iliac lymph nodes or prophylactic lymph nodes below the L5/S1 junction. We recorded second recurrence after RT and the affected site(s) in each group. We also compared disease-specific survival using uni- and multivariate analyses. RESULTS: We found no significant differences between the groups regarding second recurrence or regarding the site(s) of recurrence. We also found no significant differences in disease-specific survival between the two RT groups. However, patients who did not receive chemotherapy after the initial surgery and before RT had significantly longer survival (P=0.015). CONCLUSIONS: In patients with locally recurrent rectal or gynecological cancer, we found no significant difference in second recurrence or survival between the local tumor only RT field and the whole pelvic RT field.

Single-fraction high-dose palliative radiotherapy for facial cutaneous squamous cell carcinoma: a case report.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a common malignancy affecting the skin, and its incidence increases with age; as such, it disproportionately affects the elderly. It is especially difficult to treat advanced skin cancers in elderly patients with dementia, who may not tolerate radiotherapy. CASE DESCRIPTION: A 100-year-old woman with advanced dementia was referred to dermatology for a large cSCC involving the nasal bridge and abutting the bilateral orbits. She was initially deemed a poor candidate for surgical resection, but over time the tumor grew and became increasingly destructive. Due to tumor growth causing symptoms and threatening vision, her family requested treatment. The patient was therefore referred to radiation oncology, and she received palliative radiation, using a single fraction of 16 gray (Gy) via a single electron field. Within 3 months, she had a clinical complete response, with no residual tumor and no persistent side effects from radiotherapy (RT). Ongoing follow-up revealed durable treatment response with no bothersome late toxicity. CONCLUSIONS: Single-fraction palliative radiotherapy is a suitable treatment option for durable palliation in elderly patients unable to undergo surgery and unable to tolerate conventional, fractionated RT in cases of symptomatic or rapidly-progressing non-melanoma skin cancers (NMSC). It is well-tolerated in frail patients or those with dementia.

Technical report: a high-dose-rate interstitial brachytherapy boost for residual sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive and uncommon neoplasm that arises from the mucosa of the nasal cavity or paranasal sinuses. The multidisciplinary approach that includes surgery, radiation therapy (RT), and chemotherapy has been proven to improve survival rates. However, there is no established evidence for the efficacy of further (boost) irradiation following definitive RT in SNUC patients with residual primary tumor. We describe a successful case of a patient with SNUC who had an uncontrolled primary tumor following induction chemotherapy and radical concurrent chemoradiotherapy (CCRT) and underwent a high-dose-rate interstitial brachytherapy (HDR-ISBT) boost. A 75-year-old Japanese woman with unresectable locally advanced SNUC (LA-SNUC) received induction chemotherapy followed by radical CCRT. However, because the residual primary tumor was evident after planned external beam RT, she underwent an HDR-ISBT boost, and the tumor decreased significantly. A complete response (the Response Evaluation Criteria in Solid Tumors, ver. 1.1) was achieved 2 months after brachytherapy, and the patient has been disease-free for 2 years following treatment initiation. In conclusion, an HDR-ISBT boost can be a safe and effective treatment option in patients with residual and inoperable LA-SNUC in the maxillary sinus after initial RT.

Adrenocortical Carcinoma: a Therapeutic Challenge - 44 Cases from a Single Tertiary Care Center in India.

This study was conducted among patients with adrenocortical carcinoma (ACC) to analyze their clinico-pathological profile, management outcomes, and risk factors for local recurrence, systemic metastasis, and survival. The data of patients with ACC who were managed at a single institution between January 2004 and December 2016 was retrospectively collected and analyzed using STATA 13.1. Forty-four patients with a diagnosis of ACC were included in the study. The mean age at presentation was 38.5 ± 14.6 (9-74) with a male preponderance. Functioning tumors represented 59.1% (n = 26), cortisol being the most common hormone secreted. Forty patients (90.9%) underwent surgery, 14 (35%) of whom required an en bloc resection of adjacent organs. Fifteen (37.5%) received radiation (RT) to the postoperative bed while chemotherapy and mitotane were administered in 12 (27.3%) and 9 (20.5%) respectively. The mean follow-up was 34.3 ± 32.7 months. Twelve (30%) patients developed local recurrence, 21 (55.3%) had systemic metastasis, and 15 (34.1%) expired. The mean 1-year and 5-year overall survival rates were 77% and 65.7% respectively. On multivariate analysis, patients with ENSAT stage III/IV were significantly associated with local recurrence (p = 0.011) and metastasis (p = 0.037). Age > 50 (p = 0.003) and ENSAT III/IV (p = 0.017) were significantly associated with mortality on univariate analysis but not on multivariate analysis. In our study population, patients presented at a younger age with a male preponderance. Ninety percent underwent surgery, a subset (35%) requiring resection of adjacent organs to ensure R0 resection. Patients presenting at ENSAT stage I/II have better outcomes.

Combinations of immunotherapy and radiation therapy in head and neck squamous cell carcinoma: a narrative review.

Radiation therapy and systemic therapy are the primary non-surgical treatment modalities for head and neck squamous cell carcinoma (HNSCC). Despite advances in our biologic understanding of this disease and the development of novel therapeutics, treatment resistance remains a significant problem. It has become increasingly evident that the innate and adaptive immune systems play a significant role in the modulation of anti-tumor responses to traditional cancer-directed therapies. By inducing DNA damage and cell death, radiation therapy appears to activate both innate and adaptive immune responses. Immunotherapies targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) also have yielded promising results, particularly in the recurrent/metastatic setting. In this review, we will discuss the rationale for combining radiotherapy with immunotherapy to harness the immunomodulatory effects of radiation therapy on HNSCC, as well as biomarkers for immune response. We will also review recent preclinical and clinical data exploring these combinations in various contexts, including recurrent/metastatic and locally advanced disease. Among those with locally advanced HNSCC, we will discuss clinical trials employing immunotherapy either concurrently with radiation therapy or as maintenance following chemoradiation in both the definitive and postoperative settings, with or without the use of cisplatin-based or non-cisplatin-based chemotherapy.

A narrative review of combining radiation and immunotherapy in gastroesophageal cancers.

Despite advances in chemotherapy, radiation, and surgery, prognosis in gastroesophageal cancers (GEC) remains poor. Recent studies have demonstrated that immune checkpoint inhibitors specific to the PD-1/PD-L1 axis can improve survival with dramatic durability for a subset of patients with GEC. Radiation therapy (RT) has been shown to enhance priming and anti-tumor immunogenicity. The combination of these two treatments has shown promising results acting synergistically in pre-clinical and clinical models. Much of this synergy appears linked to in-field radiation responses, but also the abscopal response where out-of-field tumors demonstrate regression. In this review, we summarize the current role of immunotherapy and radiation in GEC. We also highlight progress from preclinical studies and translational biomarker analyses that provide rationale for ongoing efforts combining immune checkpoint inhibition and radiotherapy specifically in GECs. Questions that remain unanswered in the clinic are the optimal radiation dosing, timing, and fractionation strategies to augment abscopal immune responses. Increasing recognition of the heterogeneity of immunosuppressive mechanisms that can arise in response to radiation indicates the need for novel immune checkpoint inhibitors that target beyond the PD-1/PD-L1 axis. Smartly designed prospective trials incorporating these two approaches with ongoing translational analyses will be critical in increasing the success of combinatorial radiation and immunotherapy strategies in this disease.

Delayed initiation of radiation therapy is associated with inferior outcomes for breast cancer patients with hormone receptor-negative tumors after breast-conserving surgery.

BACKGROUND: To investigate whether the interval between adjuvant chemotherapy (CT) completion and postoperative radiation therapy initiation (ICR) after breast-conserving surgery (BCS) affects ipsilateral breast tumor recurrence (IBTR) or survival. METHODS: All women who were diagnosed with invasive breast cancer and underwent BCS between 2005 and 2014 were included. In total, 1,472 patients underwent adjuvant CT followed by postoperative radiation therapy (RT) (CT+), whereas 402 patients received postoperative RT alone (CT-). Analyses were stratified by ICR and the interval between surgery and the initiation of postoperative RT (ISR) in these two cohorts. The cutoff points for treatment delay were 47 days in the CT+ cohort and 69 days in the CT- cohort. IBTR, local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS) were assessed through Kaplan-Meier (K-M) analysis. Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes. RESULTS: The median follow-up duration was 56 months. There was an association between a delay in ICR and an increase in IBTR in the CT+ group (P=0.014 for intervals ≤47 vs. >47 days). This association was confirmed by multivariate analyses [hazard ratio (HR) of 2.766; P=0.046] in the hormone receptor-negative subgroup. The 5-year cumulative incidence rates of IBTR were 1.3% and 3.3% (≤47 vs. >47 days, respectively) in the CT+ cohort. For patients in the CT- cohort, a longer delay of initiation of postoperative RT (≤69 vs. >69 days) significantly decreased DFS (HR of 6.430; P=0.002). The 5-year cumulative incidence rates of disease recurrence were 3.0% for RT starting ≤69 days after surgery and 12.6% for RT starting >69 days after surgery. CONCLUSIONS: A high IBTR rate was related to an ICR beyond 47 days. Delay of RT after CT or surgery among patients who undergo BCS should be avoided, especially among patients in the hormone receptor-negative subgroup.

Narrative review of immunotherapy and radiation therapy in elderly patients.

Cancer is primarily a disease of the elderly, but there is a disproportionate lack of data from clinical trials in this population. Oncologists tend to underdiagnose and undertreat geriatric patients with cancer, leading to poor survival outcomes. New therapies or therapeutic combinations such as immunotherapy and stereotactic body radiation therapy (SBRT) can be used in the elderly for better tumor control and survival, with fewer toxicities. The aim of this review is to describe the synergistic effects of immunotherapy and radiation therapy (RT) and to discuss the use of these therapies concurrently and/or sequentially in the elderly. To gain a fuller picture of their elderly patient's health, physicians may also consider incorporating a comprehensive geriatric assessment (CGA) to evaluate their functional capacity, cognition, physical and mental health, and social supports which we will discuss in this review. It is recommended that oncologists use geriatric assessments in their everyday practice to have better insight on their complex elderly patients, therefore providing them a higher quality of care. They should also be incorporated in clinical trials as a way to assess and include more elderly patients in the study. Ultimately, the elderly deserve to be treated with more than their chronological age in mind, and new combination therapies and use of a geriatric assessment can help achieve that.

Radiation-activated secretory proteins of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer.

Radiation therapy (RT) in combination with immune checkpoint inhibitor (ICI) represents a promising regimen for non-small cell lung cancer (NSCLC), however, the underlying mechanisms are poorly characterized. We identified a specific dose of RT that conferred tumor regression and improved survival in NSCLC models when combined with ICI. The immune-modulating functions of RT was ascribed to activated lung-resident Scgb1a1+ club cells. Importantly, mice with club cell-specific knockout of synaptosome-associated protein 23 failed to benefit from the combination treatment, indicating a pivotal role of club cell secretome. We identified 8 club cells secretory proteins, which inhibited immunosuppressive myeloid cells, reduced pro-tumor inflammation, and enhanced anti-tumor immunity. Notably, CC10, a member of club cell secretome was increased in plasma of NSCLC patients responding to the combination therapy. By revealing an immune-regulatory role of club cells, our studies have the potential to guide future clinical trials of ICI in NSCLC.