Examining cardiac toxicity in HER2-positive breast cancer patients using trastuzumab and its influencing factors at Iran Hospital.

Trastuzumab is primarily utilized in the treatment of patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. This study aimed to investigate the incidence of cardiac toxicity associated with trastuzumab in HER2-positive breast cancer patients at Iran Hospital in 2023, as well as the factors influencing this toxicity. In this cross-sectional study, 200 patients diagnosed with HER2-positive breast cancer and receiving trastuzumab were included. The criteria for heart failure in this study were defined as an ejection fraction (EF) of less than 50% or a decrease of greater than 10% in EF. Descriptive statistics, the chi-square statistical test, Fisher's exact test, and logistic regression analyses were employed to assess the variables. A p-value of less than 0.05 was deemed statistically significant. The mean age of the participants was 51.5 ± 2.5 years. The odds ratio (OR) for the variable of anthracyclines was 1.3 (95% CI: 1.2-1.4); for opium use, the OR was 2.7 (95% CI: 0.9-8.5); for diabetes, the OR was 2.7 (95% CI: 1.2-5.9); for ischemic heart disease, the OR was 3.5 (95% CI: 1.6-7.7); and for hypertension, the OR was 4.8 (95% CI: 2.1-10.7). The OR for obesity was 1.45 (95% CI: 1.01-2.18), and the OR for age was 1.10 (95% CI: 1.01-1.12). No statistically significant association was found between opium use and cardiotoxicity (p = 0.07). This research contributes to the identification of factors that may predict responses to anthracyclines and the potential for cardiotoxicities. Ultimately, this information could inform the development of more personalized treatment strategies.

Immunotherapy and radiotherapy for older patients with invasive bladder cancer unfit for surgery or chemotherapy: practical proposal by the international geriatric radiotherapy group.

The standard of care for non-metastatic muscle invasive bladder cancer is either radical cystectomy or bladder preservation therapy, which consists of maximal transurethral bladder resection of the tumor followed by concurrent chemoradiation with a cisplatin-based regimen. However, for older cancer patients who are too frail for surgical resection or have decreased renal function, radiotherapy alone may offer palliation. Recently, immunotherapy with immune checkpoint inhibitors (ICI) has emerged as a promising treatment when combined with radiotherapy due to the synergy of those two modalities. Transitional carcinoma of the bladder is traditionally a model for immunotherapy with an excellent response to Bacille Calmette-Guerin (BCG) in early disease stages, and with avelumab and atezolizumab for metastatic disease. Thus, we propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced muscle-invasive bladder cancer who are not candidates for cisplatin-based chemotherapy and surgery.

Extended dosing (12 cycles) vs conventional dosing (6 cycles) of adjuvant temozolomide in adults with newly diagnosed high-grade gliomas: a randomized, single-blind, two-arm, parallel-group controlled trial.

Purpose: Maximum safe surgical resection followed by adjuvant chemoradiation and temozolomide chemotherapy is the current standard of care in the management of newly diagnosed high grade glioma. However, there are controversies about the optimal number of adjuvant temozolomide cycles. This study aimed to compare the survival benefits of 12 cycles against 6 cycles of adjuvant temozolomide adults with newly diagnosed high grade gliomas. Methods: Adult patients with newly diagnosed high grade gliomas, and a Karnofsky performance status>60%, were randomized to receive either 6 cycles or 12 cycles of adjuvant temozolomide. Patients were followed-up for assessment of overall survival (OS) and progression-free survival (PFS) by brain MRI every 3 months within the first year after treatment and then every six months. Results: A total of 100 patients (6 cycles, 50; 12 cycles, 50) were entered. The rate of treatment completion in 6 cycles and 12 cycles groups were 91.3% and 55.1%, respectively. With a median follow-up of 26 months, the 12-, 24-, 36-, and 48-month OS rates in 6 cycles and 12 cycles groups were 81.3% vs 78.8%, 58.3% vs 49.8%, 47.6% vs 34.1%, and 47.6% vs 31.5%, respectively (p-value=.19). Median OS of 6 cycles and 12 cycles groups were 35 months (95% confidence interval (CI), 11.0 to 58.9) and 23 months (95%CI, 16.9 to 29.0). The 12-, 24-, 36-, and 48- month PFS rates in 6 cycles and 12 cycles groups were 70.8% vs 56.9%, 39.5% and 32.7%, 27.1% vs 28.8%, and 21.1% vs 28.8%, respectively (p=.88). The Median PFS of 6 cycles and 12 cycles groups was 18 months (95% CI, 14.8 to 21.1) and 16 (95% CI, 11.0 to 20.9) months. Conclusion: Patients with newly diagnosed high grade gliomas treated with adjuvant temozolomide after maximum safe surgical resection and adjuvant chemoradiation do not benefit from extended adjuvant temozolomide beyond 6 cycles. Trial registration: Prospectively registered with the Iranian Registry of Clinical Trials: IRCT20160706028815N3. Date registered: 18/03/14.

Outcomes of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone in Esophageal Squamous Cell Carcinoma Induction chemotherapy in Esophageal Squamous Cell Carcinoma.

BACKGROUND: There is still no definite conclusion regarding the effect of Induction Chemotherapy (IC) combined with concurrent Chemoradiotherapy (CRT). Thus this study was aimed to assess outcomes of IC followed By CRT versus CRT alone in Esophageal Squamous Cell Carcinoma (ESCC). METHODS: This multicenter retrospective study performed on 105 patients who underwent CRT and 73 patients who underwent IC+CRT, between January 2016 and December 2018. The primary endpoints were OS (from the date of treatment to the date of death or 3- years follow-Up). The toxicities of CRT were graded according to the National Cancer Institute Common Toxicity Criteria (version 3.0). RESULTS: one-year (73.8% vs. 53.2%) and 2-year (53.4% vs. 38.5%) OS rate of the IC+CRT group was significantly higher than that of the CRT group (p < 0.05). No statistically significant differences were observed between the IC+CRT group and the CRT group (31.5% vs. 27.4%) in terms of the 3-year OS rate (p > 0.05). In multivariate logistic regression, age<60 (OR: 1.48; CI 95% 1.02-1.97), clinical staging II (OR: 1.36; CI 95% 1.11-1.88), and the addition of IC (OR: 1.66; CI 95% 1.07-2.19) were independent prognostic factors that affected survival positively. CONCLUSION: Our data demonstrated that a combination of IC and CRT might be a promising treatment strategy to further improve OS in ESCC patients.

Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Concurrent Use of Crocin During Chemoradiation for Esophageal Squamous Cell Carcinoma.

Crocin is the major active carotenoid of saffron (Crocus sativus L.). Its pluripotent effects have led to a growing body of literature investigating its antitumor properties as well as its diverse potentials for mood stabilization, normal tissue protection, and inflammation reduction; However, there is a gap in clinical trials testing this substance in cancer patients. In this randomized, double-blind, placebo-controlled clinical trial, patients with newly diagnosed esophageal squamous cell carcinoma were randomly assigned to either 30 mg/day of crocin or placebo, prescribed during the neoadjuvant chemo-radiotherapy. The primary endpoints were pathological response and toxicity, and secondary endpoints were depression and anxiety levels and survival analysis.

The influence of patient positioning and immobilization equipment on MR image quality and image registration in radiation therapy.

INTRODUCTION: MRI is preferred for brain tumor assessment, while CT is used for radiotherapy simulation. This study evaluated immobilization equipment's impact on CT-MRI registration accuracy and MR image quality in RT setup. METHODS: We included CT and MR images from 11 patients with high-grade glioma, all of whom were immobilized with a thermoplastic mask and headrest. T1- and T2-weighted MR images were acquired using an MR head coil in a diagnostic setup (DS) and a body matrix coil in RT setup. To assess MR image quality, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were considered in some dedicated regions of interest. We also evaluated the impact of immobilization equipment on CT-MRI rigid registration using line profile and external contour methods. RESULTS: The CNR and SNR reduction was in the RT setup of imaging. This was more evident in T1-weighted images than in T2-weighted ones. The SNR decreased by 14.91% and 12.09%, while CNR decreased by 25.12% and 20.15% in T1- and T2-weighted images, respectively. The immobilization equipment in the RT setup decreased the mean error in rigid registration by 1.02 mm. The external contour method yielded Dice similarity coefficients (DSC) of 0.84 and 0.92 for CT-DS MRI and CT-RT MRI registration, respectively. CONCLUSION: The image quality reduction in the RT setup was due to the imaged region's anatomy and its position relative to the applied coil. Furthermore, optimizing the pulse sequence is crucial for MR imaging in RT applications. Although the use of immobilization equipment may decrease the image quality in the RT setup, it does not affect organ delineation, and the image quality is still satisfactory for this purpose. Also, the use of immobilization equipment in the RT setup has increased registration accuracy.

Significance of the Pretreatment Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Predicting the Response to Neoadjuvant Chemotherapy and Survival Rates in Extremity Osteosarcoma: A Multicentre Prospective Study.

OBJECTIVES: We aimed to assess the effects of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios on the response to neoadjuvant chemotherapy and survival rates in patients with extremity osteosarcoma. PATIENTS AND METHODS: Patients with high-grade osteosarcoma admitted to oncologic centers affiliated with Iran University of Medical Sciences, Tehran, Iran from 2015 to 2021 were evaluated retrospectively to assess the impact of complete blood count-related parameters on the pathologic response after neoadjuvant chemotherapy. Then, patients were followed up prospectively to evaluate the survival rates. All patients received at least three cycles of cisplatin/doxorubicin regimen, preoperatively. In this study, the cut-off values for high neutrophil-to-lymphocyte and high platelet-to-lymphocyte ratio were considered 3.28 and 128, respectively. RESULTS: One hundred eighty-six patients were enrolled. Patients with high neutrophil-to-lymphocyte ratio and high platelet-to-lymphocyte ratio had a significantly lower overall survival rates (20.7 [95% CI 18-23.5] month vs. 34.6 [95% CI 33.2-36], p = 0.003 and 21.9 [95% CI 20.2-23.6] month versus 35.3 [95% CI 33.9-36.7], p = 0.002; respectively). Moreover, disease-free survival of patients with high platelet-to-lymphocyte ratio was worse than patients with low platelet-to-lymphocyte ratio (20.4 [95% CI 18.4-22.4] month vs. 32.7 [95% CI 30.8-34.7], p = 0.02). CONCLUSION: Our study showed that neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios at the baseline can predict the survival of patients with high-grade osteosarcoma.

Total Neoadjuvant vs. Standard Perioperative Cisplatin/ Doxorubicin Chemotherapy in Patients with Extremities Osteosarcoma: A Multi-Center Cohort Study.

INTRODUCTION: Despite improvements in survival of patients with high-grade osteosarcoma after the implementation of perioperative chemotherapy, osteosarcoma remains among the most lethal cancers. Prescription of all chemotherapy courses before the surgery may provide this opportunity to eliminate micrometastases more efficiently, increase the chances of pathologic complete response and organ preserving surgery. This study aimed to compare the outcomes of total neoadjuvant chemotherapy vs. standard perioperative chemotherapy with cisplatin/doxorubicin regimen in patients with extremities osteosarcoma. METHODS: In this retrospective cohort, all patients with high-grade osteosarcoma admitted to oncologic centers affiliated to Iran University of Medical Sciences in Tehran, Iran from 2015 to 2021 were included. Organ preserving rates, pathologic responses, and survival of patients who received all six courses of cisplatin/doxorubicin regimen preoperatively were compared to those who received the regimen perioperatively. RESULTS: Sixty-three patients were enrolled (total neoadjuvant chemotherapy: 32 patients and perioperative chemotherapy: 31 patients). In total neoadjuvant chemotherapy and perioperative chemotherapy groups, favorable pathology responses (necrosis>90%) were reported in 80.6% and 15.6% of patients, respectively (p<0.001). With a median follow-up of 24 months, mean overall survival of total neoadjuvant chemotherapy and perioperative chemotherapy groups were 21.29 months (95% CI; 19.3-23.27) and 23.46 months (95% CI; 22.7-24.1), respectively (p=0.2). The mean disease-free survival of patients in total neoadjuvant chemotherapy and perioperative chemotherapy groups were 19.54 months (95% CI; 17.0-22.0) and 21.37 months (95% CI; 19.4-23.2), respectively (p=0.2). CONCLUSION: Our results showed that prescription of all courses of doxorubicin/cisplatin chemotherapy prior to surgery can increase favorable pathologic response rates, although this improvement is not translated into overall and disease-free survival benefits.

Outcome of Second Line Treatment of Recurrent High- Grade Glioma by re-Irradiation or Bevacizumab-based Chemotherapy: A Cross Sectional Study.

INTRODUCTION: Currently, there is no standard of treatment for the management of the recurrent high-grade glioma. Re-resection, re-irradiation, and chemotherapy are among main treatment options without any proven efficacy. AIM: To compare the outcome of second line treatment of recurrent high-grade glioma by re-irradiation or bevacizumab-based chemotherapy. METHODS: Retrospectively, patients with the recurrent high-grade glioma treated by re-irradiation (ReRT group) (34 patients) or bevacizumab-based chemotherapy (Bev group) (40 patients) as the first-file after the first recurrence were compared in term of first-line progression free survival (PFS), second-line PFS, and overall survival (OS). RESULTS: Both groups were similar in term of gender (p=0.859), age (=0.071), type of first-line treatment (p=0.227), and performance status (p=0.150). With a median follow-up of 31 months (m), mortality rate was 41.2% and 70% in the ReRT and Bev groups, respectively. In the Bev and ReRT groups, median OS was 27 m (95% confidence interval (CI) 20-33.9 m) vs. 132 m (95% CI 52.9-211 m) (p<0.0001), median first-line PFS was 11 m (95% CI 7.14-28.7 m) vs. 37 m (95% CI 8.42-65.75 m) (p<0.0001), and median second-line PFS was 7 m (95% CI 3.9-10 m) vs. 9 m (95% CI 5.5-12.4 m) (p=0.564), respectively. CONCLUSION: The PFS is similar after the second line treatment of recurrent primary central nervous system malignancies either by re-irradiation or bevacizumab-based chemotherapy.

A Randomized, Controlled, Parallel-Group, Trial on the Long-term Effects of Melatonin on Fatigue Associated With Breast Cancer and Its Adjuvant Treatments.

OBJECTIVE: Cancer related fatigue is a distressing condition and correlated with decrease in quality of life of patients with malignant conditions. In continuation of our previous research, we assessed long term anti-fatigue effects of melatonin in patients with the breast cancer. MATERIAL AND METHODS: In this clinical trial, 92 breast cancer patients were randomly assigned to receive either melatonin (18 mg/day) or placebo from 1 week before the adjuvant treatments until 2 years after their completion. The levels of fatigue were assessed before and after intervention using Brief Fatigue Inventory (BFI) and were compared at a significance level of P ≤ .05. RESULTS: The BFI scores were similar between the 2 groups at the baseline (placebo group: 5.56 ± 1.59 and melatonin group: 5.72 ± 1.68, P = .67). After the intervention, not only the mean fatigue score was significantly lower in melatonin group (2.93 ± 1.04 vs 1.99 ± 1.02, P < .001, P ≤ .05), but also a greater reduction in fatigue score in intervention group was evident over time (P ≤ .001). CONCLUSION: Long-term usage of melatonin even after completion of adjuvant therapies in women with breast cancer decreased the levels of fatigue associated with the malignant condition and its treatments. THE TRIAL REGISTRY NAME AND URL, AND REGISTRATION NUMBER: Iranian Registry of Clinical Trials, https://en.irct.ir/trial/62267, IRCT20180426039421N3.

The Relationship between Lung and Heart Two-Dimensional Parameters and Three-Dimensional Dose-Volume Data in Adjuvant Radiotherapy for Breast Cancer.

Background: Two-dimensional (2D) radiographic parameters have been used to estimate the amount of heart and lung irradiated for minimizing heart and lung complications in breast cancer patients. The aim of this study was to investigate the correlation between traditionally used 2D radiographic and dose-volume parameters during adjuvant radiotherapy of breast cancer. Methods: In this cross-sectional study, we analyzed 121 female patients treated with breast-conserving surgery (BCS) or modified radical mastectomy (MRM) and 3D conformal radiotherapy (3DCRT) using two-field radiotherapy (2FRT) or three-field radiotherapy (3FRT) technique. All patients underwent computed tomography (CT)-planning. Two-D parameters, including central lung distance (CLD), maximum lung depth (MLD), maximum heart length (MHL), maximum heart distance (MHD), and chest wall separation (CWS), were measured using digitally reconstructed radiographs (DRR) and CT images. DVHs for lung, heart, and target were created. The Pearson correlation test was used to evaluate the correlation between 2D radiographic and dose-volume parameters. Results: There was a correlation between CLD and ipsilateral lung V5-20Gy and Dmean and between MLD and ipsilateral lung V5-20Gy. In 2FRT, only moderate correlation between CLD and ipsilateral lung V20Gy (r = 0.453, P = 0.003) and between MLD and ipsilateral lung V20Gy (r = 0.593, P <0.001) were observed. Poor correlation of MHL and heart V25Gy (r = 0.409, P = 0.007) was seen only in 3FRT. There was a correlation between MHD and heart dose-volume data, with a strong correlation between MHD and heart V5-25Gy and Dmean (r = 0.875-0.934, P<0.001) in the 2FRT group. No correlation between CWS and breast Dmax was found. Conclusion: There was a correlation between 2D parameters (i.e., CLD, MLD, and MHD) and the heart and lung dose-volume parameters during adjuvant breast radiotherapy. Although CLD was correlated to ipsilateral lung V5-20Gy and Dmean, the correlation between CLD and ipsilateral lung V20Gy was greater than other dose-volume parameters. MHD provided a close estimation of heart dose-volume parameters.

Predictive Value of Endoscopic Observations and Biopsy After Neoadjuvant Chemoradiotherapy in Assessing the Pathologic Complete Response of Patients With Esophageal Squamous Cell Carcinoma.

Introduction: No standard method has been defined to evaluate the therapeutic response of esophageal cancer to neoadjuvant chemoradiotherapy (CRT). This study aimed to determine the predictive value of endoscopic evaluation and biopsy after CRT in predicting the complete pathological response to neoadjuvant CRT in patients with esophageal squamous cell carcinoma (SCC). Materials and Method: This prospective, descriptive study was conducted on patients with stage II and III esophageal SCC who could undergo esophagectomy. Patients underwent neoadjuvant CRT. Four to six weeks after the end of treatment, re-endoscopy was performed and a biopsy was taken in the presence of a tumor lesion. In the absence of a tumor lesion, the marked site of the esophagus was removed as a blind biopsy. Gastrologist observations during endoscopy and the result of the pathological examination of an endoscopic biopsy were recorded. The patient underwent esophagectomy. The pathology obtained from endoscopic biopsy was compared with the pathology response obtained from esophagectomy. Results: Sixty-nine patients were included in the study, of which 32 underwent esophagectomy. In an endoscopic examination after CRT, 28 patients had macroscopic tumor remnants and 4 patients did not. Pathological examination of the samples obtained from endoscopy showed no tumor remnants in 10 patients (31.3%), and in 22 patients (68.7%), living tumor remnants were seen in the biopsy specimen. Pathologic evaluation of the samples obtained by surgical resection showed that in 13 patients, there were no viable carcinomas in the esophagus or lymph nodes removed, and the rate of pathologic complete response was 40.6. Sensitivity, specificity, positive predictive, and negative predictive values of endoscopic observations were 94.7, 23, 64.2, and 75%, respectively. Preoperative biopsy sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 68.4, 30.7, 59, and 40%, respectively. Conclusion: Considering the negative and positive predictive values of endoscopic observations and biopsy after neoadjuvant CRT, it seems that these two methods alone are not suitable for assessing the pathologic complete response after neoadjuvant treatment.

Clinical Characteristics and Outcomes of COVID-19 in 1294 New Cancer Patients: Single-Center, Prospective Cohort Study from Iran.

OBJECTIVE: To determine the clinical characteristics and outcomes of COVID-19 in a large cohort of new cancer patients referred to an oncology clinic in the north of Iran. METHODS: During the 20-month COVID-19 pandemic, new cancer patients were followed-up. Demographic, pathologic, and clinical variables were collected for each patient. COVID-19 was confirmed based on a positive polymerase chain reaction test. Analyses were performed using the STATA version 14.0 at a significance level of 0.05. RESULTS: In this study, 1294 new cancer patients were followed for 24 months (mean age: 58.7 years [range 10-95]). During the study period, COVID-19 was diagnosed in 9.4% of the patients with hospitalization rate of 3.4%, an ICU admission rate of 0.7%, and COVID-19 mortality rate of 4.9%. Hematological malignancies (ORU= 2.6, CI95% 1.28-5.34), receiving palliative treatments (ORA=3.03, CI95% 1.6-5.45) and receiving radiotherapy (ORA=2.07, 1.17-3.65) were the most common predictive factors of COVID infection in cancer patients. Also, the COVID mortality was higher in brain cancer patients (p = 0.07), metastatic disease (p = 0.01) and patients receiving palliative treatments (p = 0.02). CONCLUSION: In patients suffering from cancer, COVID-19 infection can be predicted by cancer type, palliative care, and radiotherapy in cancer patients. Furthermore, brain cancers, metastasis, and palliative care were all associated with COVID-19-related mortality.

COVID-19 Vaccination in Patients With Malignancy; A Systematic Review and Meta-Analysis of the Efficacy and Safety.

Background: Data on the efficacy and safety of COVID-19 vaccines in patients with malignancy are immature. In this paper, we assessed the literature involving the use of COVID-19 vaccines in cancer patients and reported the seroconversion rates as the main outcome and severity of COVID-19 infection and side effects following COVID-19 vaccination as the secondary outcomes. Methods: A systematic review with meta-analysis was performed. Searches were conducted in electronic websites, databases, and journals, including Scopus, PubMed, Embase, and Web of Science from January 01, 2019, to November 30, 2021. Studies reporting data on the safety and efficacy of COVID vaccine in cancer patients using any human samples were included. The risk of bias was assessed using the NEWCASTLE-OTTAWA scale in the included studies. Results: A total of 724 articles were identified from databases, out of which 201 articles were duplicates and were discarded. Subsequently, 454 articles were excluded through initial screening of the titles and abstracts. Moreover, 41 studies did not report the precise seroconversion rate either based on the type of cancer or after injection of a second dose of COVID vaccine. Finally, 28 articles met all the inclusion criteria and were included in this systematic review. The overall seroconversion rates after receiving a second dose of COVID-19 vaccine, based on type of cancer were 88% (95% CI, 81%-92%) and 70% (95% CI, 60%-79%) in patients with solid tumors and hematologic malignancies, respectively. Conclusion: Overall, we conclude that vaccination against COVID-19 in patients with active malignancies using activated and inactivated vaccines is a safe and tolerable procedure that is also accompanied by a high efficacy.

A Cohort Study on the Immunogenicity and Safety of the Inactivated SARS-CoV-2 Vaccine (BBIBP-CorV) in Patients With Breast Cancer; Does Trastuzumab Interfere With the Outcome?

Aim: To determine the efficacy and safety of inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with breast cancer. Methods: In this multi- institutional cohort study, a total of 160 breast cancer patients (mean age of 50.01 ± 11.5 years old) were assessed for the SARS-CoV-2 Anti-Spike IgG and SARS-CoV2 Anti RBD IgG by ELISA after two doses of 0.5 mL inactivated, COVID-19 vaccine (BBIBP-CorV). All patients were followed up for three months for clinical COVID-19 infection based on either PCR results or imaging findings. Common Terminology Criteria for Adverse Events were used to assess the side effects. Results: The presence of SARS-CoV-2 anti-spike IgG, SARS-CoV2 anti-RBD IgG, or either of these antibodies was 85.7%, 87.4%, and 93.3%. The prevalence of COVID-19 infection after vaccination was 0.7%, 0% and 0% for the first, second and third months of the follow-up period. The most common local and systemic side-effects were injection site pain and fever which were presented in 22.3% and 24.3% of patients, respectively. Discussion: The inactivated SARS-CoV-2 vaccine (BBIBP-CorV) is a tolerable and effective method to prevent COVID-19.

Stereotactic Body Radiotherapy and Immunotherapy for Older Patients with Oligometastases: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from local treatments such as surgery or stereotactic body radiotherapy (SBRT). However, to prevent further spread of disease, systemic treatment such as chemotherapy, targeted therapy, and hormonal therapy may be required. Older patients (70 years old or above) or physiologically frail younger patients with multiple co-morbidities may not be able to tolerate the conventional chemotherapy due to its toxicity. In addition, those with a good performance status may not receive optimal chemotherapy due to concern about toxicity. Recently, immunotherapy with checkpoint inhibitors (CPI) has become a promising approach only in the management of program death ligand 1 (PD-L1)-positive tumors. Thus, a treatment method that elicits induction of PD-L1 production by tumor cells may allow all patients with oligometastases to benefit from immunotherapy. In vitro studies have demonstrated that high dose of radiotherapy may induce formation of PD-L1 in various tumors as a defense mechanism against inflammatory T cells. Clinical studies also corroborated those observations. Thus, SBRT, with its high precision to minimize damage to normal organs, may be a potential treatment of choice for older patients with oligometastases due to its synergy with immunotherapy. We propose a protocol combining SBRT to achieve a minimum radiobiologic equivalent dose around 59.5 Gy to all tumor sites if feasible, followed four to six weeks later by CPI for those cancer patients with oligometastases. All patients will be screened with frailty screening questionnaires to identify individuals at high risk for toxicity. The patients will be managed with an interdisciplinary team which includes oncologists, geriatricians, nurses, nutritionists, patient navigators, and social workers to manage all aspects of geriatric patient care. The use of telemedicine by the team may facilitate patient monitoring during treatment and follow-up. Preliminary data on toxicity, local control, survival, and progression-free survival may be obtained and serve as a template for future prospective studies.