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This is the second part of the guidelines on the management of bone metastases. In the first part, the diagnosis and management of uncomplicated bone metastases have been addressed. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications. The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. Diffuse bone metastases may lead to hypercalcaemia that can be fatal if untreated. The growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment if oligometastatic or systemic treatment for diffuse bone metastases to try to avoid the development of SRE. ispartof: RADIOTHERAPY AND ONCOLOGY vol:173 pages:240-253 ispartof: location:Ireland status: published

After liver and lungs, bone is the third most common metastatic site (Nystrom et al., 1977). Almost all malignancies can metastasize to the skeleton but 80% of bone metastases originate from breast, prostate, lung, kidney and thyroid cancer (Mundy, 2002). Introduction of effective systemic treatment in many cancers has prolonged patients' survival, including those with bone metastases. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications, such as pain and neurologic compromise. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. In turn, growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment avoiding development of SRE. The treatment for bone metastases should focus on relieving existing symptoms and preventing new ones. Radiotherapy is the standard of care for patients with symptomatic bone metastases, providing durable pain relief with minimal toxicity and reasonable cost-effectiveness. Historically, the dose was prescribed in one to five fractions and delivered using simple planning techniques. While 3D-conformal radiotherapy is still widely used for treating bone metastases, introduction of highlyconformal radiotherapy techniques such as stereotactic body radiotherapy (SBRT) have opened new therapeutic possibilities that should be considered in selected patients with bone metastases. ispartof: RADIOTHERAPY AND ONCOLOGY vol:173 pages:197-206 ispartof: location:Ireland status: published

In 2018, Polish Society of Radiation Oncology formed a young section (yPTRO), dedicated to radiation oncologists under the age of 40. To evaluate their current situation, an anonymous, nationwide, online survey was carried out. Thirty-two-item-based questionnaire investigated young radiation oncologists’ perception of employment, workload, education, malpractice lawsuits, scientific research, and board exam. A total of 44 physicians responded to the questionnaire, yielding a response rate of 25%. Results of the survey identified the main problematic areas. In general, young radiation oncologists in Poland are overloaded with bureaucracy. They complain on spending too much time at work and lack work-life balance. The risk of being sued for medical error is threatening two-thirds of responders in everyday work. Compensation is not satisfying for nearly half of the survey participants. Nearly all young radiation oncologists continue education and participate in national and international educational events. Forty-eight percent of responders do scientific research alongside clinical work. However, the perception of young radiation oncologists on the board exam is alarming and requires further discussion. Fifty-five percent of the survey participants think that current form of the exam is not appropriate. Hopefully, 75% of physicians feel fairly evaluated. The presented report is the first of its kind in Poland. Issues mentioned in our questionnaire will help newly formed yPTRO to develop strategic priorities for the upcoming years.

Highlights • Professional quality of life is crucial for oncology professionals. • Alexythymia and empathy affect the individual capacity to cope with stress. • Alexythimia has a negative impact on radiation therapists’ professional quality of life. • Higher empatic concern increases the quality of professional well-being. • This data may help targeting professionals at risk to implement preventive strategies., Background and purpose Physical and mental well-being are crucial for oncology professionals as they affect performance at work. Personality traits, as alexithymia and empathy, may influence professional quality of life. Alexithymia involves diminished skills in emotion processing and awareness. Empathy is pertinent to the ability to understand another’s ‘state of mind/emotion’. The PROject on Burn-Out in RadiatioN Oncology (PRO BONO) investigates professional quality of life amongst radiation oncology professionals, exploring the role of alexithymia and empathy. The present study reports on data pertinent to radiation therapists (RTTs). Material and methods An online survey targeted ESTRO members. Participants were asked to fill out 3 questionnaires for alexithymia, empathy and professional quality of life: (a) Toronto Alexithymia Scale (TAS-20); (b) Interpersonal Reactivity Index (IRI); (c) Professional Quality of Life Scale (ProQoL). The present analysis focuses on RTTS to evaluate compassion satisfaction (CS), secondary traumatic stress (STS) and Burnout and their correlation with alexithymia and empathy, using generalized linear modeling. Covariates found significant at univariate linear regression analysis were included in the multivariate linear regression model. Results A total of 399 RTTs completed all questionnaires. The final model for the burnout scale of ProQoL found, as significal predictors, the TAS-20 total score (β = 0.46, p

Highlights • 49% of 543 survey participants worked full-time from home during the COVID-19 pandemic. • Perceived productivity was lower, with associated feelings of guilt. • Anxiety and depressive symptoms were higher than normative values in Europe. • Anxiety symptoms were negatively correlated with the number of years in research. • Mental health symptoms were lower in participants with institutional health support., Introduction With the COVID-19 pandemic, individuals have been forced to follow strict social isolation guidelines. While crucial to control the pandemic, isolation might have a significant impact on productivity and mental health. Especially for researchers working in healthcare, the current situation is complex. We therefore carried out a survey amongst researchers in the field of radiation oncology to gain insights on the impact of social isolation and working from home and to guide future work. Materials and methods An online survey was conducted between March 27th and April 5th, 2020. The first part contained 14 questions intended to capture an overview of the specific aspects related to research while in isolation. The second (optional) part of the questionnaire was the validated Hospital Anxiety and Depression Scale (HADS), a self-reported measure used to assess levels of anxiety and depressive symptoms. Results From 543 survey participants, 48.8% reported to work full-time from home. The impact on perceived productivity, with 71.2% of participants feeling less productive, caused 58% of participants to feel some level of guilt. Compared to normative data, relatively high levels of anxiety and depressive symptoms were recorded for the 335 participants who filled out the HADS questionnaire. Group comparisons found the presence of a supportive institutional program as the sole factor of statistical significance in both anxiety and depressive symptom levels. People having to work full-time on location showed higher depressive symptom levels than those working from home. Anxiety scores were negatively correlated with the number of research years. Conclusion Results of the survey showed there is a non-negligible impact on both productivity and mental health. As the radiation oncology research community was forced to work from home during the COVID-19 pandemic, lessons can be learned to face future adverse situations but also to improve work-life balance in general.

Highlights • Burnout is critical for oncology professionals, affecting quality of life and performance at work. • Alexithymia and empathy are personality traits influencing the capacity to cope with stress. • Alexithymia increases burnout among medical physicists with a negative impact at work. • Higher level of empathy are correlated to a better professional quality of life. • This data may help identifying subjects at risk to implement preventive strategies., Background and purpose The professional quality of life of radiation oncology professionals can be influenced by different contributing factors, including personality traits. Alexithymia involves deficits in emotion processing and awareness. Empathy is the ability to understand another’s ‘state of mind/emotion’. We investigated professional quality of life, including burnout, in radiation oncology, exploring the role of alexithymia and empathy and targeting the population of medical physicists (MPs), since this professional category is usually underrepresented in surveys exploring professional well-being in radiation oncology and MPs may experience professional distress given the increasing complexity of multimodal cancer care. Material and methods An online survey was addressed to ESTRO members. Participants filled out three questionnaires to evaluate alexithymia, empathy and professional quality of life: a) Toronto Alexithymia Scale (TAS-20); b) Interpersonal Reactivity Index (IRI); c) Professional Quality of Life Scale (ProQoL). Professional quality of life as per ProQoL was considered as dependent variable. The three domains of the ProQoL, namely compassion satisfaction (CS), secondary traumatic stress (STS) and burnout were correlated with alexithymia (as per TAS-20) and empathy (as per IRI with three subcategories: empathic concern, perspective taking and personal distress) and demographic/professional characteristics as independent variables. Generalized linear modeling was used. Significant covariates on univariate linear regression analysis were included in the multivariate linear regression model. Results A total of 308 medical physicists completed all questionnaires. Alexithymia as per TAS-20 was correlated to decreased CS (β = −0.25, p

Background Specific genomic profile of cutaneous melanomas is related to UVR exposure, which exerts biological and therapeutic impact. Subungual melanoma (SUM) is an exceedingly rare disease; therefore, it is not well characterized. SUM pathogenesis is not related to UVR induced DNA damage and expected to differ from other melanoma subtypes. Our study aimed to define the mutation profile of SUM in Caucasians. Materials and methods Next-generation sequencing-based genomic analysis was used to identify frequently mutated loci in 50 cancer-related genes in 31 SUM primary tumors. Results The most abundant mutations in SUM were found in KIT - in 13% of cases and NRAS - also in 13%, while BRAF - only in 3% of cases. Conclusions Our findings confirmed a high frequency of KIT and NRAS mutations in SUM, as well as a low incidence of BRAF mutations. We reported novel KRAS, CTNNB1, TP53, ERBB2, and SMAD4 mutations in SUM. Our findings provide new insights into the molecular pathogenesis of SUM.

The role of radiotherapy (RT) in the treatment of melanoma is constantly evolving. Although melanoma is considered a radioresistant tumour with great potential for repairing sub-lethal damage, RT is an important component of treatment. Indications for sole or adjuvant radiotherapy of the primary lesion are limited and include desmoplastic melanoma, the presence of satellite lesions and/or in-transit metastases, the presence of melanoma cells in blood or lymphatic vessels, infiltration of nerve trunks, recurrence after previous surgery, and locally advanced melanomas of the head and neck region, especially inoperable. In the past, the most common indication for radiotherapy in melanoma was adjuvant treatment after lymphadenectomy in patients with risk factors for nodal recurrence (large metastasis diameter, multiple nodes involved, extracapsular extension). Adjuvant radiotherapy after lymphadenectomy has been shown to almost double the local control of the disease, but it does not affect patient survival and may also lead to significant toxicity. Nevertheless, currently the recommended approach is systemic adjuvant treatment (anti-PD-1 immunotherapy with pembrolizumab or nivolumab and, in the presence of BRAF mutation, BRAF/MEK inhibitors), and RT should be reserved for situations in which there are contraindications to other adjuvant treatment. Stereotactic techniques, including radiosurgery of brain metastases, are becoming more widely used. RT could be a definitive treatment for a limited number of metastases or in cases of limited progression on systemic treatment. The effectiveness of RT can be increased by combining with hyperthermia. An increasing number of reports suggest great benefit from the combination of RT with immunotherapy. At present, there is no convincing evidence supporting the combination of RT with molecularly targeted treatment, and according to emerging data on the toxicity of such a combination it should be used with caution.

INTRODUCTION: In 2017 it was decided to revise the European Core Curriculum for Radiation Oncology/Radiotherapy to produce a 4th edition. The aims of the ESTRO curriculum are to develop comparable standards for training across Europe and to facilitate free movement of specialists across borders. It is also hoped that it will improve the level of training across Europe and will make the non-medical expert roles more explicit.MATERIALS AND METHODS: A wide range of stakeholders including National Society representatives, trainees, recently appointed specialists, members of the European Union Medical Specialists Radiotherapy section, an RTT, a radiobiologist, a physicist and lay members from ESTRO staff developed and commented on iterations of the curriculum.RESULTS: The 4th edition is based on the CanMEDS 2015 framework and identifies 14 Entrustable Professional Activities (EPAs) and the competencies required to perform these. The manager role is replaced by competencies related to leadership. The levels of proficiency required for tumour sites is defined as levels of EPAs.CONCLUSIONS: It is hoped that the inclusive method of developing the 4th edition has resulted in a document that will have utility in the wide range of environments in which radiation oncology is practised in Europe.

Survival of patients with breast cancer has increased in recent years due to the improvement of systemic treatment options. Nevertheless, the occurrence of brain metastases is associated with a poor prognosis. Moreover, most drugs do not penetrate the central nervous system because of the blood–brain barrier. Thus, confirmed intracranial progression after local therapy is especially challenging. The available methods of salvage treatment include surgery, stereotactic radiosurgery (SRS), fractionated stereotactic radiotherapy (FSRT), whole-brain radiotherapy, and systemic therapies. This narrative review discusses possible strategies of salvage treatment for progressive brain metastases in breast cancer. It covers possibilities of repeated local treatment using the same method as applied previously, other methods of local therapy, and options of salvage systemic treatment. Repeated local therapy may provide a significant benefit in intracranial progression-free survival and overall survival. However, it could lead to significant toxicity. Thus, the choice of optimal methods should be carefully discussed within the multidisciplinary tumor board.

Simple Summary Uveal melanoma is the most common intraocular cancer. The current eye-sparing treatment options include mostly plaque brachytherapy. However, the effectiveness of these methods is still unsatisfactory. In this article, we review several possible new treatment options. These methods may be based on the physical destruction of the cancerous cells by applying ultrasounds. Another approach may be based on improving the penetration of the anti-cancer agents. It seems that the most promising technologies from this group are based on enhancing drug delivery by applying electric current. Finally, new advanced nanoparticles are developed to combine diagnostic imaging and therapy (i.e., theranostics). However, these methods are mostly at an early stage of development. More advanced studies on experimental animals and clinical trials would be needed to introduce some of these techniques to routine clinical practice. Abstract Uveal melanoma is the most common intraocular malignancy and arises from melanocytes in the choroid, ciliary body, or iris. The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy. However, the efficacy of these methods is still unsatisfactory. This article reviews several possible new treatment options and their potential advantages in treating localized uveal melanoma. These methods may be based on the physical destruction of the cancerous cells by applying ultrasounds. Two examples of such an approach are High-Intensity Focused Ultrasound (HIFU)—a promising technology of thermal destruction of solid tumors located deep under the skin and sonodynamic therapy (SDT) that induces reactive oxygen species. Another approach may be based on improving the penetration of anti-cancer agents into UM cells. The most promising technologies from this group are based on enhancing drug delivery by applying electric current. One such approach is called transcorneal iontophoresis and has already been shown to increase the local concentration of several different therapeutics. Another technique, electrically enhanced chemotherapy, may promote drug delivery from the intercellular space to cells. Finally, new advanced nanoparticles are developed to combine diagnostic imaging and therapy (i.e., theranostics). However, these methods are mostly at an early stage of development. More advanced and targeted preclinical studies and clinical trials would be needed to introduce some of these techniques to routine clinical practice.

Immunotherapy (ITH) holds the possibility of tumor burden decrease after initial RECIST 1.1 defined progression. The clinical concept of treating selected patients (pts) beyond disease progression (PD) is supported by so-called pseudoprogression phenomenon. The aim of this study was to evaluate real-life practice and outcomes related to treatment beyond (RECIST) progression (TBP) in advanced melanoma patients. Of 584 subsequent melanoma pts analyzed 77 (13.2%) received TBP. In this cohort, the median time to first PD (TTFP) was 5.29 months (m), while time to second PD (TTSP)-8.02 m. On TBP 23.4% pts achieved an objective response (OR), and next 42.9%-stabilization of the disease (SD). 1st PD was reported most often as the development of a new lesion or increase ( 20%) of the diameter of three or more targets. In about 50% second PD was observed as an increase in the diameter of different targets that in 1st PD. Multimodal treatment resulted in 9.82 m TTSP, while ITH alone-4.93 m (p = 0.128). An oligoprogressive pattern of first PD was associated with longer TTSP (HR 0.55, 95% CI: 0.32-0.94). Median OS after first PD was 28.75 months and correlated with OR during TBP (HR 0.18, 95% CI: 0.004-0.76). Selected clinically fit melanoma patients, despite evidence of first radiographic progression, may benefit from continued treatment with PD-1 checkpoint inhibitors, but the findings should be validated in larger prospective trials. Multidisciplinary treatment should be offered to advanced melanoma patients, including radiosurgery or stereotactic radiotherapy of single loci progressing during immunotherapy.

Perivascular epithelioid cell tumors (PEComas) represent a family of rare mesenchymal neoplasms, some of which are malignant. There are no specific management guidelines for PEComas, and factors correlating with the disease course are not well defined. This analysis aimed to describe the outcomes of PEComa patients treated radically, including those treated exclusively in the national reference sarcoma center. The secondary aim of the study was to analyze factors associated with PEComa treatment efficacy. We performed an analysis of 27 patients subsequently treated radically for PEComa between 1999 and 2019 who were in follow-up in the national sarcoma reference center. The proportional-hazards model was used to compare the risk of death. The median age at diagnosis was 45 (21–67) years, and 67% of patients were female. The median follow-up period was 68 months (95% CI: 39–101). At the time of analysis, eleven patients (40.7%) experienced progression of the disease and four (14.8%) died. Surgery in the reference sarcoma center was associated with a longer disease control (log-rank p &lt, 0.001). The 5-year-OS rate was 88% (95% CI: 74–100) for the whole analyzed group. We concluded that PEComa treatment should be managed in reference sarcoma centers by a multidisciplinary tumor board with an experienced surgical team. Microscopically radical resection is associated with a longer disease-free survival. Patients requiring long-term follow-ups as late recurrence may be expected.

The basic principle for the diagnosis of melanoma metastases in the brain should be the management of multidisciplinary teams including at least a neurosurgeon, radiotherapist and clinical oncologist experienced in the treatment of melanoma and melanoma metastases in the CNS. Detection of brain lesions is associated with poor prognosis; metastases in the brain are the cause of death in 20–50% patients, and symptomatic tumours are a direct cause of death in about 90% patients. Treatment of melanoma with CNS metastases may include local management and/or systemic and symptomatic treat­ment. In the last 5 years, 10 new advanced melanoma drugs have been registered in Europe. Two-drug therapy anti-PD-1 and anti-CTLA-4 (nivolumab with ipilimumab) is the treatment of choice for asymptomatic melanoma metastases in the brain, while in the presence of BRAF mutations and asymptomatic metastases systemic treatment with BRAFi and MEKi may be the first-choice treatment.

Background This trial evaluated whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were superior to chemoradiation in rectal cancers with clinical (c)T4 or fixed cT3. Previously, we reported early results showing no differences in the radical surgery rate (primary end point). In the short-course/CCT group, we observed lower acute toxicity of preoperative treatment and better overall survival (OS). We updated results to determine whether the benefit in OS was sustained and to evaluate late complications. Patients and methods Patients with cT4 or fixed cT3 rectal cancer were randomized either to preoperative 5 × 5 Gy and three cycles of FOLFOX4 or to chemoradiation (50.4 Gy with bolus 5-Fu, leucovorin and oxaliplatin). Results Patients (N = 515) were eligible for analysis, 261 in the short-course/CCT group and 254 in the chemoradiation group. The median follow-up was 7.0 years. The difference in OS was insignificant [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.70–1.15; P = 0.38). However, the difference in early OS favouring short-course/CCT previously reported was observed again, being 9% at 3 years (95% CI 0.5% to 17%). This difference disappeared later; at 8 years OS was 49% in both groups. There was no difference in disease-free survival (HR 0.95; 95% CI 0.75–1.19; P = 0.65) at 8 years 43% versus 41% in the short-course/CCT group versus the chemoradiation group, respectively. The corresponding values for cumulative incidences of local failure and distant metastases did not differ and were HR = 1.08, 95% CI 0.70–1.23, P = 0.60, 35% versus 32% and HR = 1.10, 95% CI 0.68–1.23, P = 0.54, 36% versus 34%, respectively. The rate of late complications was similar (P = 0.66), grade 3+ being 11% versus 9% in the short-course/CCT group versus the chemoradiation group, respectively. Conclusion The superiority of preoperative short-course/CCT over chemoradiation was not demonstrated. Clinical trial number The trial is registered as ClinicalTrials.gov number NCT00833131.

MPNST is a malignant neoplasm of peripheral nerves, usually arising in connection with nerve trunks of the limbs and torso. It can develop de novo or on the basis of an already existing neurofibroma. Such tumours constitute about 5% of soft tissue sarcomas. In 90%, they occur in patients in the 2–5 decade of life. The main risk factor for this cancer is type 1 neurofibromatosis (von Recklinghausen disease). The radical surgical treatment — tumour excision, within the limits of healthy tissues (wide local excision), combined with adjuvant radiotherapy, is of primary importance in the treatment of MPNST. In cases of metastatic disease, palliative chemotherapy is used, using doxorubicin or doxorubicin with ifosfamide. Clinical improvement after chemotherapy is observed in approximately 25–30% of patients. Considering the development of molecular biology research of MPNST, one can hope for development of inhibitors that show greater effectiveness than typical chemotherapy in these patients in the near future. Currently, clinical trials with pembrolizumab, nivolumab in combination with ipilimumab, pexidartinib (KIT inhibitor, CSF1R and FLT3) in combination with sirolimus, sapanisertib (TORC 1/2 inhibitor) or LOXO-195 (inhibitor of neurotrophic tyrosine kinase inhibitors NTRK type 1, 2 and 3) are performed in MNSNT patients.

Surgery is the standard treatment of all patients with an adult type, localized soft tissue sarcoma. The wide excision is followed by radiation therapy as the standard treatment of high-grade (G2–3), deep, > 5 cm lesions. The goal of (neo)adjuvant radiation therapy is to improve local control, avoid amputation and preserve tissue by limiting the extent of resection. There is no consensus on the current role of adjuvant chemotherapy in localized soft tissue sarcoma. Given the conflicting results of trials and meta-analyses, neoadjuvant chemotherapy can be proposed as an option to the high-risk individual patient.

Clear cell sarcoma (CCS), also referred as to melanoma of soft tissues, is a rare malignant tumour of soft tissues. This tumour harbors the characteristic features of soft tissue sarcoma (STS) and is a slowly growing, painless tumour, which then acquires an aggressive course. CCS is characterized by a translocation t(12; 22)(q13; q12), which in addition to the diagnostic implications may be important for targeted treatment in the future. CCS occurs mainly on the limbs, most often shin (in feet and ankle area) in the tendons and aponeurosis, often at a young age. CCS is characterized by high potential to develop metastases in regional lymph nodes (about 30% of cases). In the diagnostic process one should consider performing a sentinel node biopsy with possible subsequent radical lymphadenectomy in the case of metastases detection. Treatment of localized disease is limited to radical local excision with complementary radiotherapy. Due to the resistance to classical chemotherapy and the presence of characteristic molecular abnormalities, trials of molecular targeted therapies in this group of cancers are ongoing. In clinical trials, MET inhibitors, tyrosine kinase inhibitors (TKI) — sunitinib and pazopanib were evaluated. CCS was also one of the subtypes of tumours evaluated in the CREATE clinical trial with crizotinib.

Purpose/objective(s) Soft tissue sarcomas (STS) is a large group of rare cancers which present high intratumoral heterogeneity. Thus, the assessment of response to the neoadjuvant treatment applied for locally advanced STS remains a challenge. We hypothesized that the pathological response (PR) could be predicted using biomarkers of the tumor microenvironment, hypoxia, and DNA damage. Materials/methods We analyzed prospectively collected core biopsy tissue samples from patients who received preoperative 5 × 5 Gy with doxorubicin-ifosfamide for marginally resectable high-grade STS in a phase II clinical trial. We have chosen tumor-infiltrating macrophages (TAMs) and intratumoral microvascular density (IMVD) as biomarkers for the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF1A) expression was selected as a biomarker of intratumoral hypoxia. Double-strand DNA breaks were evaluated by expression of the phosphorylated form of H2A histone family member X (gH2AFX). Immunohistochemical analysis (CD163, CD68, CD105, CD34, HIF1A, gH2AFX) was evaluated by experienced sarcoma pathologists blinded to sample identification with a semi-quantitative method. We scored TAMs by counting the number of positive-staining macrophages per mm2: 0-none, 1-low, and 2-high. IMVD were counted in five randomly selected fields at 200x magnification (∼6.9 mm2), and a total number of microvessels included scoring scale: 1 (1-25), 2 (26-50), 3 (51-100), and 5 (> 500). HIF1A and gH2AFX were assessed in H-score scale, including intensity: 0-none, 1-weak, 2-moderate, 3-strong, and percentage of stained cells in each category (range: 0-300). All markers were studied preoperatively, while HIF1A was additionally assessed in postoperative tissues to define hypoxic microenvironment shift after therapy. PR to the treatment was classified using the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group recommendations; grades A, B, C indicated good PR, whereas D and E suggested poor PR. Spearman rank correlation was used to measure the degree of association between biomarkers and PR. Results Nineteen patients were eligible for the analysis. We identified a good treatment PR in four cases (grades A = 1, B = 2, C = 1, D = 11, E = 4). High tumor infiltration with TAMs and high IMVD did not correlate with PR. High initial expression of HIF1A correlated with poor PR, whereas high expression of gH2AFX correlated with better PR (Tab. 1). We also confirmed decreased HIF1A expression after therapy between biomarkers and PR. Conclusion HIF1A (hypoxia degree) and gH2AFX (DNA damage extent) are candidate biomarkers for PR's prediction after neoadjuvant treatment in STS. Further evaluation in prospective studies is warranted.

Simple Summary The recommended management of marginally resectable or unresectable soft tissue sarcomas is an attempt of neoadjuvant therapy. The use of neoadjuvant chemotherapy is limited in low-grade tumors, sarcomas with chemoresistant pathology or in unfit patients. There is a growing evidence on hypofractionated radiotherapy in soft tissue sarcomas, but its efficacy may be limited by radioresistance that is frequently associated with chemoresistance. Regional hyperthermia is a potent and minimally invasive radiosensitizer. We aimed to investigate the feasibility of moderately hypofractionated radiotherapy combined with regional hyperthermia in aforementioned clinical situations. Our findings indicate that proposed combination is feasible while maintaining good short-term local efficacy and tolerance. It could serve as a basis for further studies on radiotherapy with hyperthermia in soft tissue sarcomas. Abstract Introduction: Management of marginally resectable or unresectable soft tissue sarcomas (STS) in patients who are not candidates for neoadjuvant chemotherapy due to chemoresistant pathology or contraindications remains a challenge. Therefore, in these indications, we aimed to investigate a feasibility of 10x 3.25 Gy radiotherapy combined with regional hyperthermia (HT) that could be followed by surgery or 4x 4 Gy radiotherapy with HT. Materials and methods: We recruited patients with locally advanced marginally resectable or unresectable STS who (1) presented chemoresistant STS subtype, or (2) progressed after neoadjuvant chemotherapy, or (3) were unfit for chemotherapy. The primary endpoint was the feasibility of the proposed regimen. Results: Thirty patients were enrolled. All patients received the first part of the treatment, namely radiotherapy with HT. Among them, 14 received the second part of radiotherapy with HT whereas 13 patients underwent surgery. Three patients did not complete the treatment protocol. The feasibility criteria were fulfilled in 90% of patients. Two patients developed distant metastases. One patient died due to distant progression. One patient developed rapid local recurrence after surgery. Conclusions: Hypofractionated radiotherapy with HT is a feasible treatment for marginally resectable or unresectable STS in patients who are not candidates for chemotherapy. Results of this clinical trial support the further validation of RT and HT combinations in STS.

(1) Background: Radiation-induced sarcomas (RIS) are rare diseases with poor prognoses. The aim of the study was to analyze outcomes and identify factors affecting survival in a cohort of patients with RIS. (2) Methods: We included consecutive patients with RIS that we found in the available electronic medical records of a sarcoma tertiary center. We analyzed patients’ RIS characteristics, management of RIS, the occurrence of local recurrence and distant metastases, the date of disease progression, the date of death, and the date of the last follow-up. (3) Results: Fifty-eight patients met the inclusion criteria. The most frequent sites of RIS development were the thorax and pelvis. The majority of RIS were poorly differentiated, high-grade tumors. Forty patients underwent surgery or radiotherapy with curative intent. The others were referred to palliative chemotherapy. Median progression-free survival and overall survival were 15 and 21 months, respectively. Treatment with curative intent and tumor localization on breasts and upper extremities were associated with a lower risk of death in univariate analysis. (4) Conclusions: The study confirms the poor prognosis of RIS. Treatments with locally curative intent at the tumor site are of prognostic value. Secondary radiotherapy is rarely used in RIS.

Background: There is currently no consensus on optimal management of patients with primary or recurrent non-resectable/residual retroperitoneal sarcomas (RPS). The objective of this study was to document the outcomes of patients with primary or recurrent non-resectable/residual RPS treated in our center with definitive radiotherapy (RT) and to perform a systematic review on the topic. Methods: A retrospective analysis of consecutive RPS patients treated in our center between 2000 and 2019 was performed. All consecutive patients who underwent definitive conformal RT with image guidance for primary or recurrent non-resectable or macroscopically residual RPS were included. Additionally, a systematic review compliant with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed. Results: The study enrolled 14 patients who met the aforementioned criteria. Data on clinicopathological characteristics, RT and response to treatment were assessed. RT allowed achieving prolonged local control of the disease, i.e. no local progression of the disease for more than 12 months after RT in 10 patients. Local control lasted more than 24 months in 6 cases, with minimal or no toxicity. A systemic review of 11 studies revealed concordance of our results with previous reports of primary or recurrent non-resectable/residual RPS. Conclusions: RT provided satisfactory local disease control with acceptable treatment tolerance in patients with primary or recurrent non-resectable/residual RPS and represents a valuable treatment modality in the selected group of patients. Additional RT modalities i.e. BT, particle therapy, MRI-guided RT, or GRID/Lattice RT may be introduced to improve local control and further minimize toxicity.

Background: Due to the rarity of osteosarcoma and limited indications for radiotherapy (RT), data on RT for this tumor are scarce. This study aimed to investigate the utilization of RT for osteosarcomas in the recent 20 years and to identify factors related to patients’ response to radiation. Methods: We performed a retrospective analysis of patients irradiated for osteosarcoma treatment. We planned to assess differences in the utilization of RT between the periods of 2000–2010 and 2011–2020, identify the risk factors associated with local progression (LP), determine whether RT-related parameters are associated with LP, and calculate patients’ survival. Results: A total of 126 patients with osteosarcoma who received 181 RT treatments were identified. We found a difference in RT techniques between RT performed in the years 2000–2010 and that performed in the years 2011–2020. LP was observed after 37 (20.4%) RT treatments. Intent of RT, distant metastases, and concomitant systemic treatment affected the risk of LP. Five-year overall survival was 33% (95% confidence interval (26%–43%)). Conclusions: RT for osteosarcoma treatment has evolved from simple two-dimensional palliative irradiation into more conformal RT applied for new indications including oligometastatic and oligoprogressive disease. RT may be a valuable treatment modality for selected patients with osteosarcoma.

Mucosal melanoma is a rare disease epidemiologically and molecularly distinct from cutaneous melanoma developing from melanocytes located in mucosal membranes. Little is known about its therapy. In this paper, we aimed to evaluate the results of immunotherapy and radiotherapy in a group of patients with advanced mucosal melanoma, based on the experience of five high-volume centers in Poland and Italy. There were 82 patients (53 female, 29 male) included in this retrospective study. The median age in this group was 67.5 (IQR: 57.25&ndash, 75.75). All patients received anti-PD1 or anti-CTLA4 antibodies in the first or second line of treatment. Twenty-three patients received radiotherapy during anti-PD1 treatment. In the first-line treatment, the median progression-free survival (PFS) reached six months in the anti-PD1 group, which was statistically better than 3.1 months in the other modalities group (p = 0.004). The median overall survival (OS) was 16.3 months (CI: 12.1&ndash, 22.3) in the whole cohort. Patients who received radiotherapy (RT) during the anti-PD1 treatment had a median PFS of 8.9 months (CI: 7.4&ndash, NA), whereas patients treated with single-modality anti-PD1 therapy had a median PFS of 4.2 months (CI: 3.0&ndash, 7.8), this difference was statistically significant (p = 0.047). Anti-PD1 antibodies are an effective treatment option in advanced mucosal melanoma (MM). The addition of RT may have been beneficial in the selected subgroup of mucosal melanoma patients.

Introduction: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas. The main objective of the study was to assess the efficacy of hypofractionated radiotherapy (RT) in the preoperative setting in patients with locally advanced primary MLPS. Methods: Single-arm prospective exploratory clinical trial enrolled MLPS patients for preoperative 5 &times, 5 Gy RT with delayed surgery. The endpoints of the study were the rate of early wound healing complications and 5-year local control rate. Results: 29 patients (pts) were included, all had tumors located on the lower limb. The median maximum size of the tumor was 13 cm (IQR 10&ndash, 15 cm). Early RT tolerance was good. Postoperative wound complications occurred in 11 pts (37.9%), late complications concerned 13.8% of patients. A total of 27 patients were included for the efficacy analyses. The pathological features of response to RT were detected in all analyzed surgical specimens. In 25 patients R0 margins were achieved, two patients had an R1 resection. None of the patients had local recurrence. Conclusion: Preoperative hypofractionated RT with a prolonged gap between RT and surgery is a feasible method of the management of MLPS, providing a good local control and low rates of treatment toxicity.

Purpose There is no standard treatment for marginally resectable soft tissue sarcomas (STSs) of the extremities and trunk wall, and current approaches produce unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5 × 5 Gy hypofractionated radiotherapy can generate a higher ratio of limb-sparing or conservative surgeries with negative microscopic margins (R0) and acceptable treatment toxicity. Methods and Materials We conducted a single-arm prospective clinical trial. Treatment combined 1 cycle of AI with subsequent 5 × 5 Gy radiotherapy within 1 week, followed by 2 cycles of AI and surgery. The primary endpoint was to assess the number of patients in whom en bloc R0 resection was achieved. Results Forty-six patients met the eligibility criteria. Three patients had resectable lung metastases at baseline. Forty-two received the planned protocol treatment. In 2 patients, the treatment was prematurely stopped because of the toxicity of chemotherapy. One patient died of septic shock because of severe bone marrow suppression after the second AI cycle; a second death was not related to treatment for STS. Three patients underwent amputation. In 72% of patients in the intention-to-treat analysis, we achieved en bloc R0 resections. Grade 3+ Common Terminology Criteria for Adverse Events 4.03 chemotherapy toxicity requiring dose reduction or treatment interruption occurred in 15 patients. Wound complications occurred in 18 patients, but they were severe in only 6 patients. Conclusions Preoperative AI combined with 5 × 5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. Further evaluation of this strategy is warranted.

Objective: Aim of the manuscript is to discuss how to improve margins in sacral chordoma.Background: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery.Methods: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed.Results: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment.Conclusion: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background and purpose: Different factors may influence the professional quality of life of oncology professionals. Among them, personality traits, as alexithymia and empathy, are underinvestigated. Alexithymia is about deficits in emotion processing and awareness. Empathy is the ability to understand another's 'state of mind'/emotion. The PROject on BurnOut in RadiatioN Oncology (PRO BONO) assesses professional quality of life, including burnout, in the field of radiation oncology and investigates alexithymia and empathy as contributing factors.Material and methods: An online survey was conducted amongst ESTRO members. Participants completed 3 validated questionnaires for alexithymia, empathy and professional quality of life: (a) Toronto Alexithymia Scale; (b) Interpersonal Reactivity Index; (c) Professional Quality of Life Scale. The present analysis, focusing on radiation/clinical oncologists, evaluates Compassion Satisfaction (CS), Secondary Traumatic Stress (STS) and Burnout and correlates them with alexithymia and empathy (empathic concern, perspective taking and personal distress) with generalized linear modeling. Significant covariates on univariate linear regression analysis were included in the multivariate linear regression model.Results: A total of 825 radiation oncologists completed all questionnaires. A higher level of alexithymia was associated to decreased CS (beta:-0.101; SE: 0.018; p Conclusions: Alexithymic personality trait increased burnout risk, with less professional satisfaction. Empathic concern was associated to increased stress, without leading to burnout, resulting in higher professional fulfillment. These results may be used to benchmark preventing strategies, such as work-hour restrictions, peer support, debriefing sessions, and leadership initiatives for professionals at risk. (c) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 147 (2020) 162-168

Purpose Solitary fibrous tumors (SFTs) are extremely rare mesenchymal malignancies. Given the lack of large prospective studies on radiation therapy (RT) with definitive and/or palliative intent in SFT patients, this retrospective study aimed to better define the benefit of RT in this disease. Methods and Materials A retrospective observational study was performed across 7 sarcoma centers. Clinical information was retrieved from all patients receiving RT without surgery over the course of their locally advanced and/or metastatic disease. Differences in treatment characteristics between subgroups were tested using analysis-of-variance tests. Local control (LC) and overall survival (OS) rates were calculated as time from the start of RT until local progression and death from any cause, respectively. Results Since 1990, a total of 40 patients were identified. RT was applied with definitive intent in 16 patients and with palliative intent in 24. The median follow-up period was 62 months. In patients treated with definitive RT (receiving approximately 60 Gy), the objective response rate was 67%. At 5 years, the LC rate was 81.3%, and the OS rate was 87.5%. In the case of palliative RT (typically 39 Gy), the objective response rate was 38%. The LC and OS rates at 5 years were 62.5% and 54.2%, respectively. In both subgroups, RT-associated toxicities were mild with predominantly grade 1 acute and late side effects. Conclusions This retrospective study suggests a clinically meaningful benefit for RT given with either definitive or palliative intent without surgery in SFT management. Prospective registries potentially in collaboration with patient advocacy groups are warranted to further assess the role of RT in patients with this rare malignancy.

e21541 Background: Immunotherapy (ITH) holds the possibility of tumor burden decrease after initial RECIST defined progression (PD). Clinical concept of treating of selected patients (pts) beyond PD is supported by this pseudoprogression phenomenon. The aim of this study was to evaluate real-life practice and outcomes related to treatment beyond progression (TBP) in melanoma patients. Methods: We evaluated advanced melanoma pts who started anti-PD1 treatment between 12/2015 and 12/2018 and identified pts who received TBP and had subsequent imaging to evaluate the tumor burden. Survival analyses were performed using the Kaplan-Meier method, Log-rank, chi-square and Fisher exact tests were used for comparison between groups. Data cut-off was 02/2021. Results: Of 399 subsequent melanoma pts treated, 57 (14%) patients received TBP. Anti-PD1 was 1st line treatment in 61.4% and 2nd line - in 38.6% of patients. 71.9% patients were diagnosed with skin, 7.0% - mucosal and 21.1% with FPI melanoma and 47.4% were BRAF mutated, 56.1% were male and 12.3% had 3 or more metastatic sites at treatment initiation. In this cohort median time to 1st PD (TTFP) was 4.43 months(m), while to 2nd PD (TTSP) – 8.01 m. On TBP 26.3% pts achieved objective response (OR), and next 42.1% - SD. 1st PD was reported most often as increase in 3 or more targets or one new lesion – both 22.8%; and in 24.6% cases involved central nervous system. In 56.8% second PD was observed in the same targets as 1st PD. 61.4% patients received multimodal treatment of ITH combined with radiation therapy – in 49.1%, surgery - 5.3% and both - 7.0%. There was no correlation of TTSP with gender, ECOG, initial disease stage or TNM, BRAF mutation, number of metastatic sites or pattern of progression. Multimodal treatment resulted in 13.6 m TTSP, while ITH alone - 8.0 m (p = 0.056). 1st line OR correlated with DCR on TBP while TTFP > 6 m correlated with TTSP (HR = 0.53, 95%CI 0.28-0.99). Patients with 1st line CR – had median TTSP 16.4 m, with PR – 23.5 m, while those with PD – 5.1 m. Median OS after 1st PD was 26 months and correlated with OR on TBP. Conclusions: Selected clinically fit melanoma patients despite evidence of first radiographic progression may benefit from continued treatment with PD-1 inhibitors. Multidisciplinary treatment should be offered to these patients including radiosurgery or stereotactic radiotherapy of progressing loci. Molecular biomarkers of TTSP should be analyzed in prospective studies.

e21521 Background: Merkel cell carcinoma (MCC) is an uncommon, aggressive neuroendocrine skin cancer. The prognosis in the unresectable and metastatic setting is very poor. Distant metastases develop in more than 30%. Chemotherapy (CHT), the previous mainstay of treatment, is associated with the high response rates (RR) of limited duration. The main cytotoxic drugs have been platinum derivatives, taxoids, anthracyclines, and etoposide. The standard systemic treatment for this disease has changed in the last few years. Immunotherapy (IO) is currently the basis of systemic therapy in the metastatic setting. This study aimed to analyze outcomes for unresectable and metastatic MCC pts treated in routine clinical practice, mostly before the era of IO availability. Methods: We conducted the retrospective analysis of data from 36 MCC pts in unresectable (n= 23) and metastatic (n=13) settings treated in three oncological centers, diagnosed between 01/2010 and 12/2019, with data cut-off on 31/12/2020. The data collected included epidemiological and clinical information. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Results: The median patient age at diagnosis was 72 years (57-88); 58.3% were male. The most common primary tumor (PT) locations were lower limbs (41.7%), head and neck (30.6%), and upper limbs (16.7%). In 63.9% the PT was located in the sun-exposed skin. The most common location of distant metastases were nonregional lymph nodes (n=9) and lungs (n=3). Thirty-six pts received 1st line CHT with the median progression-free survival (mPFS) of 5.3 months (95%CI 2.88-7.7) and objective response of 61.1%, with 13.9% complete responses (CR). The most commonly used regimens were platinum-based and anthracycline-based regimens (n=26). Disease progression (PD) was observed in 91.7% of pts treated with 1st line CHT. Twenty-one pts received 2nd line therapy, IO (n=14), or CHT (n=7), with PD in 19 pts (90.6%), mPFS 2.83 months (95% CI 0.59-5.06) and RR of 33.3% (0% CR). 13 pts were treated with avelumab (AVE), all in the 2nd line, with RR of 38.5% (0% CR). The mPFS in the 2nd line was 5 months (95%CI 0-11.46) on AVE compared to 2.82 (95%CI 0.46-5.19) on CHT (HR 0.65, 95%CI 0.25-1.70, p=0.378). During 1st line systemic therapy, 16 pts underwent palliative surgery (n=7, 19.4%) or received radiation therapy (RT) (n=9, 25%), and during 2nd line, one patient was treated with surgery, and five pts received RT. The median overall survival was 10.38 months (95% CI 2.90-17.87). Local treatment did not improve the treatment outcomes in the 1st (p=0.119) nor 2nd line (p=0.821). Conclusions: Our results confirm the poor prognosis of pts with unresectable and metastatic MCC. The response rates and median PFS for CHT in the 1st and 2nd line setting are consistent with historical data. The treatment with AVE in the 2nd line allows achieving better results, similar to the results reported in the clinical trials.

e21566 Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease includes surgery (SUR) and radiotherapy (RTH) to achieve high locoregional control rates. The sentinel lymph node biopsy (SLNB) is recommended procedure in cases without clinical nodal involvement. In selected cases, chemotherapy (CHT) may also be considered, but its role is not confirmed. This study aimed to analyze outcomes for locally advanced MCC pts treated in routine clinical practice. Methods: We conducted the retrospective analysis of data from 156 MCC pts treated with curative surgery in four oncological centers, diagnosed between 01/2010 and 12/2019, with data cut-off on 31/12/2020. The data collected included epidemiological and clinical information. Survival analyses were performed using the Kaplan-Meier method, log-rank test and multivariate Cox regression. Results: The median patient age at diagnosis was 72 years (30-94); 50.6% were male. The primary tumor (PT) locations were lower limbs (33.3%), upper limbs (30.1%), and head and neck (28.2%). MCC with no PT was diagnosed in 3.9%. In 62.0% the PT was located in the sun-exposed skin. The median tumor size was 25 mm (4-170). Lymph node (LN) involvement (clinical or positive SLNB or LND) at diagnosis was found in 26.9% (n = 42). The scar excision was done in 50.0% (positive in 16.6%), SLNB in 36.5% (positive in 10.5 %), 51.9% of pts received perioperative treatment, including RTH- 86.4%, CHT- 21%. The relapse rate was 38.3% (35.8% local-regional, 11.1% distant). With the median follow-up of 2.2-years, the median disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were not reached. The 1-year DFS, LRFS and DMFS rates were 65%, 68%, and 90%. The negative independent risk factors for DFS were male gender (HR 1.42, 95%CI 1.06-3.01), metastases in LN at diagnosis (HR 5.41, 95%CI 2.39-12.26), no SLNB in pts with no clinical metastases in LN (HR 5.45, 95%CI 2.41-12.3), and no perioperative RTH (HR 2.19, 95%CI 1.29-3.76). The median overall survival (OS) was 6.9 years (95%CI 4.64-9.15). The negative independent risk factors for OS were male gender (HR 1.95, 95%CI 1.16-3.27), age above 70 (HR 2.0, 95%CI 1.15-3.48), metastases in LN at diagnosis (HR 3.15, 95%CI 1.49-6.68), and no SLNB in pts with no clinical metastases in LN (HR 2.30, 95%CI 1.10-4.82). PT location, UV-exposure, and perioperative CHT or RTH were not independent risk factors for OS. Conclusions: Our results confirm that the MCC treatment should be done in an experienced multidisciplinary team. Male gender, nodal involvement at diagnosis, and no SLNB in pts without clinical metastases in LN are associated with poor prognosis in DFS and OS. The perioperative RTH improves the treatment outcomes and reduces disease progression risk but does not impact OS. Perioperative CHT does not affect pts survival.

Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients' quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical trials are strongly needed to provide more efficacious therapies.

Background: Randomized trials have shown a lower efficacy of postoperative chemotherapy in rectal cancer patients having received preoperative radiotherapy than in nonirradiated colorectal cancer (CRC) patients. We hypothesized that preoperative radio(chemo)therapy impairs the relative dose intensity (RDI) of further chemotherapy because of long-term radiation damage. This retrospective study aimed to test this hypothesis. Methods: The analysis was conducted on 220 consecutive patients with CRC who received FOLFOX-4 postoperatively or because of cancer relapse. Of these, 41 patients with rectal cancer had preoperatively received radio(chemo)therapy (study group) and the remaining 179 with CRC had not (control group). The RDI of oxaliplatin at 8 and 16 weeks was calculated. Results: The median RDI of oxaliplatin at 8 weeks was 95.91% in the study group and 96.15% in the control group (p = 0.79). The corresponding percentages at 16 weeks were 87.6 and 86.5%, respectively (p = 0.55). It was found that within 0–8 weeks, 26.9% of the patients in the study group and 26.3% in the control group had grade 3+ toxicity, hypersensitivity reactions, or granulocyte colony-stimulating factor administration (p = 0.94). The corresponding percentages for 0–16 weeks were 44.8 and 43.9%, respectively (p = 0.92). Conclusions: We found no association between preoperative radio(chemo)therapy and the RDI of FOLFOX-4. We failed to explain the inferior efficacy of postoperative chemotherapy in patients with rectal cancer who had preoperatively received irradiation compared to those with CRC who had not.