Ablative doses of stereotactic body radiotherapy (SBRT) may improve pancreatic cancer outcomes but may carry greater potential for gastrointestinal toxicity. Rucosopasem, an investigational selective dismutase mimetic that converts superoxide to hydrogen peroxide, can potentially increase tumor control of SBRT without compromising safety. GRECO-2 is a phase II, multicenter, randomized, double-blind, placebo-controlled trial of rucosopasem in combination with SBRT in locally advanced or borderline resectable pancreatic cancer. Patients will be randomized to rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT fraction (5 x 10 Gy). The primary end point is overall survival. Secondary end points include progression-free survival, locoregional control, time to metastasis, surgical resection rate, best overall response, in-field local response and acute and long-term toxicity. The use of high doses of radiation delivered directly to tumors (stereotactic body radiation therapy [SBRT]) may improve survival compared with lower doses of radiation in patients with pancreatic cancer, but it may increase side effects. Rucosopasem, an investigational new drug being developed, can potentially improve the ability of SBRT to treat tumors without decreasing safety. In a previous study, median overall survival was improved when patients were treated with SBRT plus avasopasem, a drug that works the same way as rucosopasem. GRECO-2 is a clinical trial of rucosopasem used in combination with SBRT for treatment of localized pancreatic cancer. Patients will be randomly selected to receive either rucosopasem 100 mg or placebo via intravenous infusion over 15 min, before each SBRT treatment. The main result being studied is overall survival. Additional results include amount of time before tumors start to grow, how often patients get tumors surgically removed, best overall response and long-term safety.Clinical Trial Registration: NCT04698915 (ClinicalTrials.gov)

Trial-in-progress NCT04476797 CONCLUSION: GC4711 may improve the benefit-risk ratio of 5-fraction SBRT in early-stage NSCLC; improving tumor control while reducing the risk of lung injury.

TPS4184 Background: While treatment of pancreatic cancer has advanced, survival rates remain low. Stereotactic body radiotherapy (SBRT; high dose per fraction radiation) may exhibit improved clinical outcomes in locally advanced pancreatic cancer but carries potential gastrointestinal toxicity risks (Zhong 2017). Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically converts superoxide to hydrogen peroxide (Riley 2006). Studies have shown that normal cells tolerate hydrogen peroxide fluxes better than cancer cells (Doskey 2016). As radiation response modifiers, dismutase mimetics have the potential to increase tumor control of SBRT without compromising radiation safety (El-Mahdy 2020, Sishc 2021). In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT. Improvements versus placebo were also observed in local tumor control, time to metastases, and progression-free survival. Altogether, these data support the hypothesis that rucosopasem may improve survival and the benefit-risk ratio of SBRT by improving efficacy without increasing gastrointestinal toxicity. Materials/Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet. Approximately 160 patients will be randomized (approximately 35 sites) to receive rucosopasem 100 mg or placebo via IV infusion over 15 minutes, prior to each SBRT fraction (5 x 10 Gy). Patients judged to be resectable will undergo surgical exploration within 8 weeks after SBRT. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, locoregional control, time to metastasis, surgical resection rate, RO resection rate, best overall response, in-field local response, and safety (acute and late toxicities). Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial is now enrolling. Clinical trial information: NCT04698915.

Integrated breast cancer care is complex, marked by multiple hand-offs between primary care and specialists over an extensive period of time. Communication is essential for treatment compliance, lowering error and complication risk, as well as handling co-morbidity. The director role of care, however, becomes often unclear, and patients remain lost across departments. Digital tools can add significant value to care communication but need clarity about the directives to perform in the care team. In effective breast cancer care, multidisciplinary team meetings can drive care planning, create directives and structured data collection. Subsequently, nurse navigators can take the director’s role and become a pivotal determinant for patient care continuity. In the complexity of care, automated AI driven planning can facilitate their tasks, however, human intervention stays needed for psychosocial support and tackling unexpected urgency. Care allocation of patients across centres, is often still done by hand and phone demanding time due to overbooked agenda’s and discontinuous system solutions limited by privacy rules and moreover, competition among providers. Collection of complete outcome information is limited to specific collaborative networks today. With data continuity over time, AI tools can facilitate both care allocation and risk prediction which may unveil non-compliance due to local scarce resources, distance and costs. Applied research is needed to bring AI modelling into clinical practice and drive well-coordinated, patient-centric cancer care in the complex web of modern healthcare today.

TPS4670 Background: Local progression causes up to 30% of deaths from pancreatic cancer (PC) and is also a significant source of morbidity. Stereotactic body radiotherapy (SBRT) offers the potential for improved therapeutic index over standard fractionation, but current regimens of 5 fractions of 5-7 Gy/fraction are constrained by nearby organ tolerance and offer only palliation without improving survival. Safe dose escalation may be necessary to improve SBRT efficacy. Avasopasem, a superoxide dismutase mimetic, selectively converts superoxide (O2•-) to hydrogen peroxide (H2O2) and oxygen. O2•-initiates normal tissue damage due to RT. Avasopasem is in a Phase 3 trial (NCT03689712) to reduce RT-induced oral mucositis in head and neck cancer, based on positive results in a randomized Phase 2 trial for that indication (Anderson, JCO 2019). Avasopasem improved the survival of mice receiving 8.5 Gy x 5 to the upper abdomen. Cancer cells are less tolerant to elevated H2O2, and more tolerant to elevated O2•-, than normal cells, and avasopasem demonstrated mechanism-dependent synergy with high dose-fraction RT in a human tumor xenograft with inducible expression of catalase (Sishc, AACR 2018). Thus, adding avasopasem to SBRT may increase both the efficacy and the safety of the latter. Methods: 48 patients with locally advanced PC, who have completed medically-indicated induction chemotherapy, are randomized 1:1 to placebo or avasopasem, 90 mg IV, prior to each of 5 consecutive daily (M-F) SBRT fractions. A phase I/II Late Onset Efficacy/ Toxicity tradeoff (LO-ET) based adaptive design adaptive model drives assignment of SBRT dose escalation in each arm based on a dual endpoint (Gr 3-4 GI toxicity or death; local stable disease or better) by 90 days post SBRT. The planned dose levels are 10, 11 and 12Gy x 5 fractions (BED10 = 100,112.5 and 132Gy, respectively) as an integrated boost to the gross tumor volume (GTV). Primary endpoint: Maximum tolerated dose of SBRT with avasopasem or placebo. Secondary endpoints progression-free survival, response rate, and acute (90 day) and late (12 month) radiation toxicity with avasopasem vs placebo. Exploratory correlative studies include ctDNA, tumor exome/transcriptome sequencing, and immune profiling. Clinical trial information: NCT03340974 .

Local progression of PC causes substantial morbidity & mortality. High dose SBRT is limited by GI tract toxicity. RT forms superoxide (O2•-) causing normal tissue toxicity; another RT product, OH•, causes cancer cell death. GC4419, a selective superoxide dismutase mimetic, converts O2•- to H2O2, which is more toxic to cancer vs normal tissue, while not decreasing OH•. GC4419 was synergistic with hypofractionated RT in multiple in vivo tumor models, while protecting normal tissue. We hypothesized GC4419, already in Phase 3 trials for another indication (NCT03689712), might improve the clinical benefit-risk ratio of high dose SBRT.

Introduction: Hodgkin lymphoma (HL) survivors are known to suffer from an excess risk of cardiac disease (CD) due to radiation and anthracyclines. However, CD is also associated with other risk factors. The purpose of the study was to evaluate the impact of treatment and patient characteristics on the risk of subsequent CD in the EORTC (European Organisation for Research and Treatment of Cancer)-GELA (Groupe d'Étude des Lymphomes de l'Adulte, now LYSA) cohort of HL patients treated in 9 randomized trials from 1964 to 2004 (n = 6658). Methods: Incidence of CD was reported during follow-up and through a patient-reported questionnaire (LSQ), mailed in 2009 to 2010 (56.7% of all patients alive with known address). Comorbidities were registered at LSQ completion. A multivariate Cox proportional hazards regression model on first CD, stratified by trial, was fitted on treatment variables (mean radiation dose to the heart and cumulative doses of anthracyclines and vinca-alkaloids) as well as patient characteristics at treatment start (age, gender, country, gender*age, smoking, family history of CD, BMI). Model reduction was performed with the backward selection procedure at a 5% threshold level. Estimated hazard ratios (HRs) were presented with their 95% confidence intervals (CI) and tested at the 5% two-sided significance level. Data from H1 to H8 trials were used to build the model; the model validation was performed based on H9 trial data using measures of discrimination (C-index). Results: A total of 1919 patients responded to the LSQ, 49% were males and the median age at treatment start was 29 years (range, 10-69). A total of 85.9% had early-stage disease, and 1293 patients received both radiotherapy and anthracyclines. The median duration of follow-up was 14 years (range, 5-44). A total of 416 patients (21.7%) reported CD events. The model built included mean radiation dose to the heart (HR = 1.02 per Gy increase; 95% CI, 1.00-1.03; P = .019), cumulative dose of anthracyclines (HR = 1.17 per 100 mg/m2 increase; 95% CI, 1.00-1.37; P = 0.05), age (HR = 1.04 per year increase; 95% CI, 1.03-1.05; P < .001), and BMI (HR = 1.05; 95% CI, 1.02-1.09; P < .001). The resulting linear predictor was LP = [0.017 × heart dose] + [0.002 × dose anthracyclines] + [0.037 × age] + [0.053 × BMI]. The C-index was moderate at 0.57 (95% CI, 0.39-0.74). There was a strong association between CD and post-treatment smoking and comorbidities such as high blood pressure, high cholesterol levels, diabetes, and elevated BMI. Conclusions: Following treatment for HL, the subsequent risk of CD is influenced by radiation dose to the heart, the cumulative dose of anthracycline but not vinca-alkaloids, and age and BMI at treatment start. However in this cohort of HL patients, the overall cardiac risk is only partly explained by treatment exposure. The poor model performance (low C-index) may be explained by important posttreatment events such as later occurrence of established cardiac risk factors. Keywords: Hodgkin lymphoma (HL)

Hodgkin lymphoma (HL) survivors are known to suffer from an excess risk of cardiac disease (CD) due to radiation and anthracyclines. However, CD is also associated with other risk factors such as high blood pressure (BP), elevated levels of blood cholesterol (BChol), diabetes mellitus (DM), obesity, and smoking. For HL survivors, the effects of these factors have been difficult to quantify as it requires information from patients treated decades ago. The purpose of our study was to quantify the degree of association between traditional cardiac risk factors and incidence of CD in the EORTC (European Organisation for Research and Treatment of Cancer)-GELA (Groupe d'Étude des Lymphomes de l'Adulte, now LYSA) cohort of HL patients treated in nine randomized trials from 1964 to 2004 (n = 6,658). Incidence of CD was reported during follow-up and through a patient-reported questionnaire (LSQ), mailed in 2009-2010 to patients known to be alive and for whom an address was known (56.7% of the patients enrolled in all trials). The degree of association of CD with cardiac risk factors reported at LSQ completion was measured using the Mantel-Haenszel estimate of the common odds ratio (OR) across trials with its 95% confidence interval (CI). The P-value was obtained from the Cochran-Mantel-Haenszel test. Heterogeneity of OR across trials was assessed using the Breslow-Day Test. One thousand nine hundred nineteen patients responded to the LSQ, 49% were males and the median age at treatment start was 29 years (range: 10-69 years). The median duration of follow-up was 14 years (range: 5-44 years). A total of 416 patients (21.7%) reported CD events. At LSQ completion, 329 (17.1%) survivors reported high BP, 376 (19.6%) elevated BChol, 96 (5.0%) DM, 221 (11.5%) were obese (body mass index ≥ 30) and 289 (15.1%) were smokers. The OR for CD with high BP was 2.7 (95% CI = 2.1-3.5, P < 0.0001), with elevated BChol 2.6 (95% CI = 2.0-3.4, P < 0.0001), with DM 3.5 (95% CI = 2.3-5.5, P < 0.0001), with obesity 1.3 (95% CI = 0.9-1.8, P = 0.173) and with smoking 1.3 (95% CI = 0.9-1.7, P = 0.149). Heterogeneity of OR across trials was significant for high BP (P = 0.007). For HL patients, the continued efforts to limit treatment exposure are important for minimizing subsequent cardiac risk. In addition, traditional lifestyle risk factors such as high BP, elevated BChol, and DM are significantly associated to the risk of developing CD. Although causality cannot be concluded, patient education, lifestyle intervention, and counseling should be encouraged at all treating institutions.

The 2nd International Consensus Conference for Breast Cancer in Young Women (BCY2) took place in November 2014, in Dublin, Ireland organized by the European School of Oncology (ESO). Consensus recommendations for the management of breast cancer in young women (BCYW) were updated from BCY1 with incorporation of new evidence to inform the guidelines, and areas of research priorities were identified. This manuscript summarizes these international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

BACKGROUND:Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we aimed to quantify the effect of anthracyclines, vinca-alkaloids, and radiotherapy on the risk of cardiovascular disease in patients treated for Hodgkin's lymphoma. METHODS:In 2009-10, a Life Situation Questionnaire (LSQ) was distributed to patients by mail to assess late-onset effects of Hodgkin's lymphoma treatment in patients who were included in nine successive European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA, now renamed LYSA) randomised trials between 1964 and 2004. We reconstructed the mean radiation doses to the heart and carotid arteries and the cumulative doses of anthracyclines and vinca-alkaloids for all patients. Incidence of cardiovascular disease was reported during follow-up and updated through the LSQ. We applied Cox proportional hazards regression analyses to quantify the effect of chemotherapy and radiation on the risk of a first cardiovascular disease event. FINDINGS:Information of primary treatment was complete for 6039 patients (median age at diagnosis 30 years [IQR 23-40]; median length of follow-up 9 years [6-14]). 1919 patients responded to the LSQ. 1238 first cardiovascular events were recorded in 703 patients, most were ischaemic heart disease (132 [19%]), congestive heart failure (85 [12%]), arrhythmia (110 [16%]), and valvular disease (77 [11%]). The mean heart radiation dose per 1 Gy increase (HR 1·015 [95% CI 1·006-1·024], p=0·0014) and the dose of anthracyclines per 50 mg/m(2) increase in cumulative dose (1·077 [1·021-1·137], p=0·0064) were significant predictors of cardiovascular disease. Cumulative dose of vinblastine (unadjusted model p=0·77), vincristine (p=0·36), and mean radiation dose to the left (p=0·41) or right (p=0·70) internal carotid artery did not predict for cardiovascular events. INTERPRETATION:Quantification of the increased cardiovascular risk with specific doses of radiation and anthracycline exposure will enable a quantitative assessment of the optimum combination of systemic therapy and radiation, which will help clinicians to balance the risks and benefits of different regimens for individual patients. FUNDING:Rigshospitalet Research Committee, the EORTC Cancer Research Fund, and the Sally Snowman Survivorship Fellowship.

Purpose/Objective(s)18F-fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (PET) Standardized Uptake Value (SUVmax) is a standard PERCIST variable in assessing metabolic response to cancer therapy. Here we explore the predictive value of early post-treatment SUVmax in patients receiving SDRT in extracranial oligometastatic lesions.Materials/Methods201 metastatic lesions in 93 consecutive patients (mean 2.1 lesions/patient, range 1-9) were treated before 9/2014 with image-guided SDRT to a PTV dose of 24 Gy. Tumor histologies included NSCLC (73), colorectal (49), breast (23), prostate (23), renal cell (14), bladder (9), sarcoma (4), melanoma (4), and pancreatic tumors (2). Sites of metastases were lung (68), bone (62), lymph-nodes (29), liver (21), soft tissues (13), adrenal (8). SUVmax were acquired before SDRT, at 3 months post-treatment and at every 6 months thereafter. Tumor response was scored according to the PERCIST criteria, with metabolic relapse defined as any increase of SUVmax >30% above nadir level. All metabolic relapses were confirmed by morphologic imaging. Lesions had a minimum of 2 post-treatment scans (mean 4; range 2-9). Correlation of SUVmax declines (ΔSUVmax) and actuarial local control were analyzed by recursive partitioning.ResultsAt a median follow-up of 22 months (range 6-39), 21 lesions developed PERCIST failures yielding a 3 year actuarial local relapse-free of 90%. Baseline SUVmax (median 8.9; range 1-52) did not correlate with the probability of local metabolic progression (p=0.9). At 3 months post-SDRT 18% (37/201) of the lesions had a >90% reduction in SUVmax (PERCIST complete metabolic response), and 78 lesions (38%) showed >75% (ΔSUV(>75%)). Actuarial relapse-free survival showed ΔSUV(>75%) was associated with 93% local control at 36 months vs. 77% for ΔSUV(≤75%) (p=0.02). ΔSUV(>70%) also showed significance as predictor of local control (p=0.05), but lower partitioning values were not significant. All relapses occurred within 20 months post-treatment. The actuarial 3-year PERCIST local control was 95% for lesions in bone regardless of histological subtypes, 79% for lesions in mobile organs (lung, liver, adrenal) and 75% for soft tissue and lymph node metastases.ConclusionΔSUV(>75%) at 3 months appears a predictor of durable local control in tumor lesions treated with SDRT, providing a readily accessible tool for rapid evaluation of outcome in treatment protocols exploring SDRT. Whether a more sensitive discriminator of SDRT outcome can be provided by current PET technology is yet to be established. The PERCIST outcomes by target organs indicate a need for improved tumor segmentation of lesions in soft tissue locations, and improved tumor tracking during treatment delivery in mobile target organs. Purpose/Objective(s)18F-fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (PET) Standardized Uptake Value (SUVmax) is a standard PERCIST variable in assessing metabolic response to cancer therapy. Here we explore the predictive value of early post-treatment SUVmax in patients receiving SDRT in extracranial oligometastatic lesions. 18F-fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (PET) Standardized Uptake Value (SUVmax) is a standard PERCIST variable in assessing metabolic response to cancer therapy. Here we explore the predictive value of early post-treatment SUVmax in patients receiving SDRT in extracranial oligometastatic lesions. Materials/Methods201 metastatic lesions in 93 consecutive patients (mean 2.1 lesions/patient, range 1-9) were treated before 9/2014 with image-guided SDRT to a PTV dose of 24 Gy. Tumor histologies included NSCLC (73), colorectal (49), breast (23), prostate (23), renal cell (14), bladder (9), sarcoma (4), melanoma (4), and pancreatic tumors (2). Sites of metastases were lung (68), bone (62), lymph-nodes (29), liver (21), soft tissues (13), adrenal (8). SUVmax were acquired before SDRT, at 3 months post-treatment and at every 6 months thereafter. Tumor response was scored according to the PERCIST criteria, with metabolic relapse defined as any increase of SUVmax >30% above nadir level. All metabolic relapses were confirmed by morphologic imaging. Lesions had a minimum of 2 post-treatment scans (mean 4; range 2-9). Correlation of SUVmax declines (ΔSUVmax) and actuarial local control were analyzed by recursive partitioning. 201 metastatic lesions in 93 consecutive patients (mean 2.1 lesions/patient, range 1-9) were treated before 9/2014 with image-guided SDRT to a PTV dose of 24 Gy. Tumor histologies included NSCLC (73), colorectal (49), breast (23), prostate (23), renal cell (14), bladder (9), sarcoma (4), melanoma (4), and pancreatic tumors (2). Sites of metastases were lung (68), bone (62), lymph-nodes (29), liver (21), soft tissues (13), adrenal (8). SUVmax were acquired before SDRT, at 3 months post-treatment and at every 6 months thereafter. Tumor response was scored according to the PERCIST criteria, with metabolic relapse defined as any increase of SUVmax >30% above nadir level. All metabolic relapses were confirmed by morphologic imaging. Lesions had a minimum of 2 post-treatment scans (mean 4; range 2-9). Correlation of SUVmax declines (ΔSUVmax) and actuarial local control were analyzed by recursive partitioning. ResultsAt a median follow-up of 22 months (range 6-39), 21 lesions developed PERCIST failures yielding a 3 year actuarial local relapse-free of 90%. Baseline SUVmax (median 8.9; range 1-52) did not correlate with the probability of local metabolic progression (p=0.9). At 3 months post-SDRT 18% (37/201) of the lesions had a >90% reduction in SUVmax (PERCIST complete metabolic response), and 78 lesions (38%) showed >75% (ΔSUV(>75%)). Actuarial relapse-free survival showed ΔSUV(>75%) was associated with 93% local control at 36 months vs. 77% for ΔSUV(≤75%) (p=0.02). ΔSUV(>70%) also showed significance as predictor of local control (p=0.05), but lower partitioning values were not significant. All relapses occurred within 20 months post-treatment. The actuarial 3-year PERCIST local control was 95% for lesions in bone regardless of histological subtypes, 79% for lesions in mobile organs (lung, liver, adrenal) and 75% for soft tissue and lymph node metastases. At a median follow-up of 22 months (range 6-39), 21 lesions developed PERCIST failures yielding a 3 year actuarial local relapse-free of 90%. Baseline SUVmax (median 8.9; range 1-52) did not correlate with the probability of local metabolic progression (p=0.9). At 3 months post-SDRT 18% (37/201) of the lesions had a >90% reduction in SUVmax (PERCIST complete metabolic response), and 78 lesions (38%) showed >75% (ΔSUV(>75%)). Actuarial relapse-free survival showed ΔSUV(>75%) was associated with 93% local control at 36 months vs. 77% for ΔSUV(≤75%) (p=0.02). ΔSUV(>70%) also showed significance as predictor of local control (p=0.05), but lower partitioning values were not significant. All relapses occurred within 20 months post-treatment. The actuarial 3-year PERCIST local control was 95% for lesions in bone regardless of histological subtypes, 79% for lesions in mobile organs (lung, liver, adrenal) and 75% for soft tissue and lymph node metastases. ConclusionΔSUV(>75%) at 3 months appears a predictor of durable local control in tumor lesions treated with SDRT, providing a readily accessible tool for rapid evaluation of outcome in treatment protocols exploring SDRT. Whether a more sensitive discriminator of SDRT outcome can be provided by current PET technology is yet to be established. The PERCIST outcomes by target organs indicate a need for improved tumor segmentation of lesions in soft tissue locations, and improved tumor tracking during treatment delivery in mobile target organs. ΔSUV(>75%) at 3 months appears a predictor of durable local control in tumor lesions treated with SDRT, providing a readily accessible tool for rapid evaluation of outcome in treatment protocols exploring SDRT. Whether a more sensitive discriminator of SDRT outcome can be provided by current PET technology is yet to be established. The PERCIST outcomes by target organs indicate a need for improved tumor segmentation of lesions in soft tissue locations, and improved tumor tracking during treatment delivery in mobile target organs.

AIM:To review the recent evolution of spine SBRT with emphasis on single dose treatments. BACKGROUND:Radiation treatment of spine metastases represents a challenging problem in clinical oncology, because of the high risk of inflicting damage to the spinal cord. While conventional fractionated radiation therapy still constitutes the most commonly used modality for palliative treatment, notwithstanding its efficacy in terms of palliation of pain, local tumor control has been approximately 60%. This limited effectiveness is due to previous lack of technology to precisely target the tumor while avoiding the radiosensitive spinal cord, which constitutes a dose-limiting barrier to tumor cure. MATERIALS AND METHODS:A thorough review of the available literature on spine SBRT has been carried out and critically assessed. RESULTS:Stereotactic body radiotherapy (SBRT) emerges as an alternative, non-invasive high-precision approach, which allows escalation of tumor dose, while effectively sparing adjacent uninvolved organs at risk. Engaging technological advances, such as on-line Cone Beam Computed Tomography (CBCT), coupled with Dynamic Multi-Leaf Collimation (DMLC) and rapid intensity-modulated (IMRT) beam delivery, have promoted an interactive image-guided (IGRT) approach that precisely conforms treatment onto a defined target volume with a rapid dose fall-off to collateral non-target tissues, such as the spinal cord. Recent technological developments allow the use of the high-dose per fraction mode of hypofractionated SBRT for spinal oligometastatic cancer, even if only a few millimeters away from the tumor. CONCLUSION:Single-dose spine SBRT, now increasingly implemented, yields unprecedented outcomes of local tumor ablation and safety, provided that advanced technology is employed.

Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90 % of young patients with BC are symptomatic. Women <40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age <40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC <40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2 % in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient’s comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in presence of visceral metastases, unless there is concern or proof of endocrine resistance or there is a need for rapid disease response and/or symptom control. Recommendations for chemotherapy (CT) should not differ from those for older patients with the same characteristics of the metastatic disease and its extent. Young age by itself should not be an indication to prescribe more intensive and combination CT regimens over the sequential use of monotherapy. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) represent an important group of promising drugs in managing patients with breast cancer susceptibility gene (BRCA)-1- or BRCA-2-associated BC. Specific age-related side effects of systemic treatment (e.g., menopausal symptoms, change in body image, bone morbidity, cognitive function impairment, fertility damage, sexual dysfunction) and the social impact of diagnosis and treatment (job discrimination, taking care for children) should also be carefully addressed when planning systemic long-lasting therapy, such as endocrine therapy. Survivorship concerns for young women are different compared to older women, including issues of fertility, preservation, and pregnancy.

Improvements in treatment and earlier diagnosis have both contributed to increased survival for many cancer patients. Unfortunately, many treatments carry a risk of late effects including cardiovascular diseases (CVDs), possibly leading to significant morbidity and mortality. In this paper we describe current knowledge of the cardiotoxicity arising from cancer treatments, outline gaps in knowledge, and indicate directions for future research and guideline development, as discussed during the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer (EORTC). Better knowledge is needed of the late effects of modern systemic treatments and of radiotherapy to critical structures of the heart, including the effect of both radiation dose and volume of the heart exposed. Research elucidating the extent to which treatments interact in causing CVD, and the mechanisms involved, as well as the extent to which treatments may increase CVD indirectly by increasing cardiovascular risk factors is also important. Systematic collection of data relating treatment details to late effects is needed, and great care is needed to obtain valid and generalisable results. Better knowledge of these cardiac effects will contribute to both primary and secondary prevention of late complications where exposure to cardiotoxic treatment is unavoidable. Also surrogate markers would help to identify patients at increased risk of cardiotoxicity. Evidence-based screening guidelines for CVD following cancer are also needed. Finally, risk prediction models should be developed to guide primary treatment choice and appropriate follow up after cancer treatment.

Over the past decades, early diagnosis, new drugs and more personalised multi-modality treatment have led to impressive increases in survival rates of patients with cancer. This success in treating cancer has resulted in a large and rapidly increasing number of cancer survivors, yet life after cancer is often compromised by a broad spectrum of late adverse treatment effects. Some encounter cardiovascular, second malignancies, cognitive or other morbidities which impair normal life in an important way. Some patients are confronted with societal discrimination due to slower performance, chronic fatigue or partial inability and these things can adversely affect employment, education, insurance or mortgage opportunities. In 2012, the European Organisation of Research and Treatment of Cancer (EORTC) Survivorship Task Force was created to focus research efforts on late morbidity of cancer treatment and its impact on society. On 30–31st January 2014, the 1st EORTC Cancer Survivorship Summit was organised to facilitate interaction between clinicians, researchers, social workers, patients, insurers, bankers and policy makers. This important event addressed the needs of cancer survivors, and new collaborations between academic groups, patient advocates, financial and political representatives were formed to guide future European research and health policies in this field. This special issue of the European Journal of Cancer is entirely dedicated to this Summit and addresses, respectively, second malignancies, cardiovascular disease, cognitive dysfunction, infertility/sexuality and psycho-social problems following cancer treatment.