Patient-reported symptoms before adjuvant locoregional radiotherapy for breast cancer: triple-negative histology impacts the symptom burden.

BACKGROUND: Multimodal breast cancer treatment may cause side effects reflected in patient-reported outcomes and/or symptom scores at the time of treatment planning for adjuvant radiotherapy. In our department, all patients have been assessed with the Edmonton Symptom Assessment System (ESAS; a questionnaire addressing 11 major symptoms and wellbeing on a numeric scale of 0-10) at the time of treatment planning since 2016. In this study, we analyzed ESAS symptom severity before locoregional radiotherapy. PATIENTS AND METHODS: Retrospective review of 132 patients treated between 2016 and 2021 (all comers in breast-conserving or post-mastectomy settings, different radiotherapy fractionations) was performed. All ESAS items and the ESAS point sum were analyzed to identify subgroups with higher symptom burden and thus need for additional care measures. RESULTS: The biggest patient-reported issues were fatigue, pain, and sleep problems. Patients with triple negative breast cancer reported a higher symptom burden (mean 30 versus 20, p = 0.038). Patients assigned to adjuvant endocrine therapy had the lowest point sum (mean 18), followed by those on Her-2-targeting agents without chemotherapy (mean 19), those on chemotherapy with or without other drugs (mean 26), and those without systemic therapy (mean 41), p = 0.007. Those with pathologic complete response after neoadjuvant treatment had significantly lower anxiety scores (mean 0.7 versus 1.8, p = 0.03) and a trend towards lower depression scores, p = 0.09. CONCLUSION: Different surgical strategies, age, and body mass index did not impact on ESAS scores, while the type of adjuvant systemic therapy did. The effect of previous neoadjuvant treatment and unfavorable tumor biology (triple negative) emerged as important factors associated with symptom burden, albeit in different domains. ESAS data may facilitate identification of patients who should be considered for additional supportive measures to alleviate specific symptoms.

Survival after docetaxel for metastatic castration-resistant prostate cancer in a rural health care setting.

Introduction: The aim of this study was to evaluate overall survival of men who received systemic therapy with docetaxel for metastatic castration- resistant prostate cancer (MCRPC) in rural Nordland County, Norway. Prognostic factors related to treatment and other variables were evaluated. Material and methods: Overall, 132 pa- tients were included in this retrospective study covering the years 2009-2022. Uni- and multivariate survival analyses were performed. Results: In this elderly cohort (median age 72 years), weekly low-dose docetaxel was the preferred regimen (44%). Seventy-three percent were treated in the first line. Only 11 patients (8%) were pre-exposed to docetaxel in the hormone-sensitive phase. Median survival was 14.3 months. Prognostic factors for longer survival included higher hemoglobin, lower lactate dehydrogenase, administration of docetaxel as first-line MCRPC treatment, and use of fewer prescription drugs for comorbidity. Pre-exposure to docetaxel did not play a major role, p = 0.76. Conclusions: In this rural health care setting, survival after docetaxel was shorter than reported by other groups. Blood test results were confirmed as important prognostic factors. In the present era of evolving treatment sequences, we recommend monitoring of real-world treatment results.

Prospective randomized clinical studies involving reirradiation: update of a systematic review.

BACKGROUND: Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or symptom palliation, depending on disease/recurrence type and stage. The purpose of this follow-up study to a previous review from 2016 was to summarize all recently published randomized trials. Points of interest again included identifcation of methodological strengths and weaknesses, practice-changing results, and open questions. MATERIAL AND METHODS: Systematic review of trials published between 2015 and February 2023. RESULTS: We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The median number of patients was 60. Mirroring the previous review, trial design, primary endpoints and statistical hypotheses varied widely. The updated results only impact on decision making for reirradiation of nasopharynx cancer and glioma. Patients with one of these diseases, as well as other head and neck cancers, may benefit from reirradiation-induced local control, e.g. in terms of progression-free survival. For the first time, hyperfractionated radiotherapy emerged as preferred option for recurrent, inoperable nasopharynx cancer. Despite better therapeutic ratio with hyperfractionation, serious toxicity remains a concern after high cumulative total doses. Randomized trials are still lacking for prostate cancer and other sites. CONCLUSION: Multicentric randomized trials on reirradiation are feasible and continue to refine the current standard of care for recurrent disease after previous radiotherapy. Ongoing prospective studies such as the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) observational cohort ReCare (NCT: NCT03818503) will further shape the clinical practice of reirradiation.

Palliative appropriateness criteria: external validation of a new method to evaluate the suitability of palliative radiotherapy fractionation.

BACKGROUND: Recently, the palliative appropriateness criteria (PAC) score, a novel metric to aid clinical decision-making between different palliative radiotherapy fractionation regimens, has been developed. It includes baseline parameters including but not limited to performance status. The researchers behind the PAC score analyzed the percent of remaining life (PRL) on treatment. The latter was accomplished by calculating the time between start and finish of palliative radiotherapy (minimum 1 day in case of a single-fraction regimen) and dividing it by overall survival in days from start of radiotherapy. The purpose of the present study was to validate this novel metric. PATIENTS AND METHODS: The retrospective validation study included 219 patients (287 courses of palliative radiotherapy). The methods were identical to those employed in the score development study. The score was calculated by assigning 1 point each to several factors identified in the original study and using the online calculator provided by the PAC developers. RESULTS: Median survival was 6 months and death within 30 days from start of radiotherapy was recorded in 13% of courses. PRL on treatment ranged from 1 to 23%, median 8%. Significant associations were confirmed between online-calculated PAC score, observed survival, and risk of death within 30 days from the start of radiotherapy. Patients with score 0 had distinctly better survival than all other groups. The score-predicted median risk of death within 30 days from start of radiotherapy was 22% in our cohort. A statistically significant correlation was found between predicted and observed risk (p < 0.001). The original and present study were not perfectly concordant regarding number and type of baseline parameters that should be included when calculating the PAC score. CONCLUSION: This study supports the dual strategy of PRL and risk of early death calculation, with results stratified for fractionation regimen, in line with the original PAC score study. When considering multifraction regimens, the PAC score identifies patients who may benefit from shorter courses. Additional work is needed to answer open questions surrounding the underlying components of the score, because the original and validation study were only partially aligned.

Days at home in the last three months of life: patterns-of-care analysis in patients with non-small cell lung cancer.

Introduction: To calculate the number of days patients with terminal non-small cell lung cancer (NSCLC) spent at home in the last 3 months of life, and to identify factors that predict a lower proportion of days at home. Material and methods: Retrospective study of 434 deceased patients with NSCLC. The number of days spent in a hospital or nursing home was identified from electronic health records. Results: Most patients received primary chemotherapy. Only 45% received palliative care provided by a dedicated palliative care team (PCT). In the last 3 months of life, only 39 patients (9%) were not hospitalized. The median number of days spent in hospital was 17, range 0-61. Hospital death occurred in 48%. Admission to a nursing home was recorded in 45%. Overall, the patients spent a median of 64 days at home. Both, older patients and females spent fewer days at home. Family network and aspects of palliative care, possibly reflecting the symptom duration or burden, also impacted days at home. Conclusions: Long-lasting need for PCT support (not just the final 3 months) and earlier necessity for opioid analgesics were predictive for a reduced number of days at home. However, modifiable factors such as sex were identified too.

Percent of remaining life on palliative radiation treatment: solely a function of fractionation?

Background: This study analyzed the percent of remaining life (PRL) on treatment in patients irradiated for bone metastases. Bone metastases were treated together with other target volumes, if indicated, e.g. a 10-fraction treatment course that included brain and bone metastases. PRL was determined by calculating the time between start and finish of palliative radiotherapy (minimum 1 day in case of a single-fraction regimen) and dividing it by overall survival in days from start of radiotherapy. Materials and methods: Different baseline parameters were assessed for association with dichotomized PRL (< 5% vs. ≥ 5%). The retrospective study included 219 patients (287 courses of palliative radiotherapy). After univariate analyses, multi-nominal logistic regression was employed. Results: PRL on treatment ranged from 1-23%. Single-fraction radiotherapy resulted in < 5% PRL on treatment in all cases. All courses with 10 fractions resulted in at least 5% PRL on treatment. Significant associations were found between various baseline parameters and PRL category. With fractionation included in the regression model, 3 parameters retained significant p-values: Karnofsky performance status (KPS), none-bone target volume and fractionation (all with p < 0.001). If analyzed without fractionation, none-bone target volume (p < 0.001), hemoglobin (p < 0.001), KPS (p = 0.01), lack of additional systemic treatment (p = 0.01), and hypercalcemia (p = 0.04) were significant. Conclusions: Fractionation is an easily modifiable factor with high impact on PRL. Patients with KPS < 70 and those treated for additional target types during the same course are at high risk of spending a larger proportion of their remaining life on treatment.

European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus on re-irradiation: definition, reporting, and clinical decision making.

Re-irradiation can be considered for local recurrence or new tumours adjacent to a previously irradiated site to achieve durable local control for patients with cancer who have otherwise few therapeutic options. With the use of new radiotherapy techniques, which allow for conformal treatment plans, image guidance, and short fractionation schemes, the use of re-irradiation for different sites is increasing in clinical settings. Yet, prospective evidence on re-irradiation is scarce and our understanding of the underlying radiobiology is poor. Our consensus on re-irradiation aims to assist in re-irradiation decision making, and to standardise the classification of different forms of re-irradiation and reporting. The consensus has been endorsed by the European Society for Radiotherapy and Oncology and the European Organisation for Research and Treatment of Cancer. The use of this classification in daily clinical practice and research will facilitate accurate understanding of the clinical implications of re-irradiation and allow for cross-study comparisons. Data gathered in a uniform manner could be used in the future to make recommendations for re-irradiation on the basis of clinical evidence. The consensus document is based on an adapted Delphi process and a systematic review of the literature was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Palliative non-small cell lung cancer treatment and end-of-life care stratified by sex and childlessness: an important interplay in unmarried patients?

PURPOSE: To analyze the interplay of sex and presence of children in unmarried patients with non-small cell lung cancer, because previous studies suggested sex-related disparities. Adult children may participate in treatment decisions and provision of social support or home care. METHODS: Retrospective single-institution analysis of 186 unmarried deceased patients, managed according to national guidelines outside of clinical trials. Due to the absence of other oncology care providers in the region and the availability of electronic health records, all aspects of longitudinal care were captured. RESULTS: Eighty-eight female and 98 male patients were included, the majority of whom had children. Comparable proportions in all four strata did not receive active therapy. Involvement of the palliative care team was similar, too. Patients without children were more likely to receive systemic therapy (39% utilization in women with children, 67% in women without children, 41% in men with children, 52% in men without children; p = 0.05). During the last 3 months of life, female patients spent significantly more days in hospital than their male counterparts. Place of death was not significantly different. Home death was equally uncommon in each group. In the multivariate analysis, survival was associated with age and cancer stage, in contrast to sex and presence of children. CONCLUSION: In contrast to studies from other healthcare systems, unmarried male patients were managed in a largely similar fashion to their female counterparts and with similar survival outcome. Unexpectedly, patients without children more often received systemic anti-cancer treatment.

New clinical data on human spinal cord re-irradiation tolerance.

PURPOSE: To provide additional clinical data about the re-irradiation tolerance of the spinal cord. METHODS: This was a retrospective bi-institutional study of patients re-irradiated to the cervical or thoracic spinal cord with minimum follow-up of 6 months. The maximum dose (Dmax) and dose to 0.1cc (D0.1cc) were determined (magnetic resonance imaging [MRI]-defined cord) and expressed as equivalent dose in 2­Gy fractions (EQD2) with an α/ß value of 2 Gy. RESULTS: All 32 patients remained free from radiation myelopathy after a median follow-up of 12 months. Re-irradiation was performed after 6-97 months (median 15). In 22 cases (69%) the re-irradiation spinal cord EQD2 Dmax was higher than that of the first treatment course. Forty-eight of 64 treatment courses employed fraction sizes of 2.5 to 4 Gy to the target volume. The median cumulative spinal cord EQD2 Dmax was 80.7 Gy, minimum 61.12 Gy, maximum 114.79 Gy. The median cumulative spinal cord D0.1cc EQD2 was 76.1 Gy, minimum 61.12 Gy, maximum 95.62 Gy. Besides cumulative dose, other risk factors for myelopathy were present (single-course Dmax EQD2 ≥51 Gy in 9 patients, single-course D0.1cc EQD2 ≥51 Gy in 5 patients). CONCLUSION: Even patients treated to higher cumulative doses than previously recommended, or at a considerable risk of myelopathy according to a published risk score, remained free from this complication, although one must acknowledge the potential for manifestation of damage in patients currently alive, i.e., still at risk. Individualized decisions to re-irradiate after appropriate informed consent are an acceptable strategy, including scenarios where low re-irradiation doses to the spinal cord would compromise target coverage and tumor control probability to an unacceptable degree.

The LabBM score is an excellent survival prediction tool in patients undergoing palliative radiotherapy.

BACKGROUND AND AIM: The prognostic assessment of patients referred for palliative radiotherapy can be conducted by site-specific scores. A quick assessment that would cover the whole spectrum could simplify the working day of clinicians who are not specialists for a particular disease site. This study evaluated a promising score, the LabBM (validated for brain metastases), in patients treated for other indications. MATERIALS AND METHODS: The LabBM score was calculated in 375 patients by assigning 1 point each for C-reactive protein and lactate dehydrogenase above the upper limit of normal, and 0.5 points each for hemoglobin, platelets and albumin below the lower limit of normal. Uni- and multivariate analyses were performed. RESULTS: Median overall survival gradually decreased with increasing point sum (range 25.1-1.1 months). When grouped according to the original three-tiered model, excellent discrimination was found. Patients with 0-1 points had a median survival of 15.7 months. Those with 1.5-2 points had a median survival of 5.8 months. Finally, those with 2.5-3.5 points had a median survival of 3.2 months (all p-values ≤ 0.001). CONCLUSION: The LabBM score, which is derived from inexpensive blood tests and easy to use, stratified patients into three very distinct prognostic groups and deserves further validation.

Hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for multiple brain metastases.

BACKGROUND: The current study was aimed at investigating the feasibility of hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for metastases and at assessing tumor control in comparison with conventional whole-brain radiation therapy (WBRT) in patients with multiple brain metastases. METHODS: Between August 2012 and December 2016, 66 patients were treated within a monocentric feasibility trial with HA-WBRT+SIB: hippocampus-avoidance WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume ≤ 9 Gy) and a simultaneous integrated boost (51 or 42 Gy in 12 fractions) for metastases/resection cavities. Intracranial tumor control, hippocampal failure, and survival were subsequently compared with a retrospective cohort treated with WBRT via propensity score matching analysis. RESULTS: After 1:1 propensity score matching, there were 62 HA-WBRT+SIB patients and 62 WBRT patients. Local tumor control (LTC) of existing metastases was significantly higher after HA-WBRT+SIB (98% vs 82% at 1 year; P = .007), whereas distant intracranial tumor control was significantly higher after WBRT (82% vs 69% at 1 year; P = .016); this corresponded to higher biologically effective doses. Intracranial progression-free survival (PFS; 13.5 vs 6.4 months; P = .03) and overall survival (9.9 vs 6.2 months; P = .001) were significantly better in the HA-WBRT+SIB cohort. Four patients (6.5%) developed hippocampal metastases after hippocampus avoidance. The neurologic death rate after HA-WBRT+SIB was 27.4%. CONCLUSIONS: HA-WBRT+SIB can be an efficient therapeutic option for patients with multiple brain metastases and is associated with improved LTC of existing metastases, higher intracranial PFS, a reduction of the neurologic death rate, and an acceptable risk of radiation necrosis. The therapy has the potential to prevent neurocognitive adverse effects, which will be further evaluated in the multicenter, phase 2 HIPPORAD trial.

Provider decision regret-a useful method for analysis of palliative thoracic re-irradiation for lung cancer?

BACKGROUND: The overall usefulness of palliative thoracic re-irradiation depends on the balance between efficacy, survival, and toxicity, and is difficult to judge from previous studies. In the absence of patient-reported data, we developed a method for provider decision regret that addresses the question "would we re-irradiate this patient again in light of the known outcome?" Furthermore, we analyzed different reasons for decision regret and defined a subgroup at increased risk. PATIENTS AND METHODS: A retrospective analysis of 33 patients with lung cancer re-irradiated with 17-45 Gy was performed. Reasons for decision regret included re-irradiation within the last 30 days of life, immediate radiological progression after re-irradiation (as opposed to stable disease or objective response), radiation myelopathy, any grade 4-5 toxicity, grade 3 pneumonitis, and other grade 3 toxicity in the absence of a symptomatic benefit or a time period of at least 3 months without worsening of the treated tumor. RESULTS: Median survival time was 5.2 months (95% confidence interval 3.4-7.0 months). Symptomatic and radiological responses were observed. Provider decision regret was declared in 12 patients (36%): 2 patients with grade 3 pneumonitis, 3 patients with a short survival (radiotherapy during the last 30 days of life), and 7 patients with progression. Decision regret was declared only in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or 3 and was associated with a time interval to re-irradiation <6 months. CONCLUSION: Our data support the usefulness and acceptable side effects profile of palliative re-irradiation for lung cancer. Patients with reduced PS are at increased risk of futile treatment. Future research should aim at prediction of immediate disease progression (the prevailing cause of decision regret). Evaluation of provider decision regret has the potential to improve the way we learn from retrospective databases and should also be considered for other scenarios where high-quality prospective outcome data are lacking.

Adverse events in deceased hospitalised cancer patients as a measure of quality and safety in end-of-life cancer care.

BACKGROUND: Anticancer treatment exposes patients to negative consequences such as increased toxicity and decreased quality of life, and there are clear guidelines recommending limiting use of aggressive anticancer treatments for patients near end of life. The aim of this study is to investigate the association between anticancer treatment given during the last 30 days of life and adverse events contributing to death and elucidate how adverse events can be used as a measure of quality and safety in end-of-life cancer care. METHODS: Retrospective cohort study of 247 deceased hospitalised cancer patients at three hospitals in Norway in 2012 and 2013. The Global Trigger Tool method were used to identify adverse events. We used Poisson regression and binary logistic regression to compare adverse events and association with use of anticancer treatment given during the last 30 days of life. RESULTS: 30% of deceased hospitalised cancer patients received some kind of anticancer treatment during the last 30 days of life, mainly systemic anticancer treatment. These patients had 62% more adverse events compared to patients not being treated last 30 days, 39 vs. 24 adverse events per 1000 patient days (p < 0.001, OR 1.62 (1.23-2.15). They also had twice the odds of an adverse event contributing to death compared to patients without such treatment, 33 vs. 18% (p = 0.045, OR 1.85 (1.01-3.36)). Receiving follow up by specialist palliative care reduced the rate of AEs per 1000 patient days in both groups by 29% (p = 0.02, IRR 0.71, CI 95% 0.53-0.96). CONCLUSIONS: Anticancer treatment given during the last 30 days of life is associated with a significantly increased rate of adverse events and related mortality. Patients receiving specialist palliative care had significantly fewer adverse events, supporting recommendations of early integration of palliative care in a patient safety perspective.

Long-term survival results after treatment for oligometastatic brain disease.

AIM: The aim of this study was to characterize the survival results of patients with up to four brain metastases after intense local therapy (primary surgery or stereotactic radiotherapy) if extracranial metastases were absent or limited to one site, e.g. the lungs. BACKGROUND: Oligometastatic disease has repeatedly been reported to convey a favorable prognosis. MATERIAL AND METHODS: This retrospective study included 198 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. Uni- and multivariate tests were performed. RESULTS: Median survival was 16.5 months (single brain metastasis) and 9.8 months (2-4, comparable survival for 2, 3 and 4), respectively (p = 0.001). After 5 years, 15 and 2% of the patients were still alive. In patients alive after 2 years, added median survival was 23 months and the probability of being alive 5 years after treatment was 26%. In multivariate analysis, extracranial metastases were not significantly associated with survival, while primary tumor control was. CONCLUSION: Long-term survival beyond 5 years is possible in a minority of patients with oligometastatic brain disease, in particular those with a single brain metastasis. The presence of extracranial metastases to one site should not be regarded a barrier towards maximum brain-directed therapy.

Definitive, intensity modulated tomotherapy with a simultaneous integrated boost for prostate cancer patients - Long term data on toxicity and biochemical control.

AIM: To report long-term data regarding biochemical control and late toxicity of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) with tomotherapy in patients with localized prostate cancer. BACKGROUND: Dose escalation improves cancer control after curative intended radiation therapy (RT) to patients with localized prostate cancer, without increasing toxicity, if IMRT is used. MATERIALS AND METHODS: In this retrospective analysis, we evaluated long-term toxicity and biochemical control of the first 40 patients with intermediate risk prostate cancer receiving SIB-IMRT. Primary target volume (PTV) 1 including the prostate and proximal third of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. PTV 2 containing the prostate with smaller safety margins was treated as SIB to a total dose of 76 Gy with 2.17 Gy per fraction. Toxicity was evaluated using an adapted CTCAE-Score (Version 3). RESULTS: Median follow-up of living patients was 66 (20-78) months. No late genitourinary toxicity higher than grade 2 has been reported. Grade 2 genitourinary toxicity rates decreased from 58% at the end of the treatment to 10% at 60 months. Late gastrointestinal (GI) toxicity was also moderate, though the prescribed PTV Dose of 76 Gy was accepted at the anterior rectal wall. 74% of patients reported any GI toxicity during follow up and no toxicity rates higher than grade 2 were observed. Grade 2 side effects were reported by 13% of the patients at 60 months. 5-year freedom from biochemical failure was 95% at our last follow up. CONCLUSION: SIB-IMRT using daily MV-CT guidance showed excellent long-term biochemical control and low toxicity rates.

A Four-Tiered Prognostic Score for Patients Receiving Palliative Thoracic Radiotherapy for Lung Cancer.

Palliative radiotherapy improves lung cancer related symptoms. Prognosis should be taken into account when deciding about fractionation. In this study, prognostic factors derived from multivariate analysis were used to assign a point sum reflecting 6-month survival. Four prognostic groups were compared. Performance status, lactate dehydrogenase, C-reactive protein, liver/adrenal gland metastases, and extrathoracic disease status significantly predicted survival and formed the basis of the score. The four groups had a median survival of 0.8, 1.6, 3.3, and 10.5 months (6-month survival 0, 10, 30, 70%; 12-month survival 0, 0, 12, 40%; p = 0.0001), respectively. In the unfavorable group best supportive care might be preferable.

Patient-reported symptoms before palliative radiotherapy predict survival differences.

BACKGROUND: Widely used prognostic scores, e. g., for brain or bone metastases, are based on disease- and patient-related factors such as extent of metastases, age and performance status, which were available in the databases used to develop the scores. Few groups were able to include patient-reported symptoms. In our department, all patients were assessed with the Edmonton Symptom Assessment System (ESAS, a one-sheet questionnaire addressing 11 major symptoms and wellbeing on a numeric scale of 0-10) at the time of treatment planning since 2012. Therefore, we analyzed the prognostic impact of baseline ESAS symptom severity. METHODS: Retrospective review of 102 patients treated with palliative radiotherapy (PRT) between 2012 and 2015. All ESAS items were dichotomized (below/above median). Uni- and multivariate analyses were performed to identify prognostic factors for survival. RESULTS: The most common tumor types were prostate, breast and non-small cell lung cancer, predominantly with distant metastases. Median survival was 6 months. Multivariate analysis resulted in six significant prognostic factors. These were ESAS pain while not moving (median 3), ESAS appetite (median 5), Eastern Cooperative Oncology Group (ECOG) performance status, pleural effusion/metastases, intravenous antibiotics at start or within 2 weeks before PRT and no systemic cancer treatment. CONCLUSIONS: Stronger pain while not moving and reduced appetite (below/above median) predicted significantly shorter survival. Development of new prognostic scores should include patient-reported symptoms and other innovative parameters because they were more important than primary tumor type, age and other traditional baseline parameters.

Repeat reirradiation of the spinal cord: multi-national expert treatment recommendations.

BACKGROUND: Improved survival of patients with spinal bone metastases has resulted in an increased number of referrals for retreatment and repeat reirradiation. METHODS: A consortium of expert radiation oncologists (RO) has been established with the aim of providing treatment recommendations for challenging clinical scenarios for which there are no established guidelines. In this case, a patient developed local progression of a T5 vertebral lesion after two prior courses of palliative radiotherapy (time interval >12 months, assumed cumulative biologically equivalent dose in 2­Gy fractions [EQD2] for spinal cord [alpha/beta 2 Gy] 75 Gy). Expert recommendations were tabulated with the aim of providing guidance. RESULTS: Five of seven RO would offer a third course of radiotherapy, preferably with advanced techniques such as stereotactic radiotherapy. However, the dose-fractionation concepts were heterogeneous (3-20 fractions) and sometimes adjusted to different options for systemic treatment. All five RO would compromise target volume coverage to reduce the dose to the spinal cord. Definition of the spinal cord planning-organ-at-risk volume was heterogeneous. All five RO limited the EQD2 for spinal cord. Two were willing to accept more than 12.5 Gy and the highest EQD2 was 19 Gy. CONCLUSIONS: The increasing body of literature about bone metastases and spinal cord reirradiation has encouraged some expert RO to offer palliative reirradiation with cumulative cord doses above 75 Gy EQD2; however, no consensus was achieved. Strategies for harmonization of clinical practice and development of evidence-based dose constraints are discussed.

Second re-irradiation: a narrative review of the available clinical data.

BACKGROUND: Considerable controversy exists about the safety and efficacy of second re-irradiations (three courses of radiotherapy to overlapping volumes). Therefore, all published clinical studies were reviewed. MATERIAL AND METHODS: Contemporary and historical articles were identified. Outcomes such as survival, local control, symptom improvement and side effects were extracted. Contemporary results were grouped by anatomical location of the re-irradiated region in the body. RESULTS: Most data were derived from central nervous system tumors, pelvic tumors and bone metastases. We could include nine contemporary, retrospective studies with 2-25 patients each. Nearly, all patients were treated with palliative intent. Most of the prescribed re-irradiation regimens were highly individualized and thus difficult to compare. Symptomatic responses were recorded in most patients. In palliatively treated patients with pelvic and bony target volumes, high-grade toxicity was uncommon. CONCLUSIONS: Despite of issues related to study size, length of follow-up and calculation of lifetime cumulative equivalent dose, the available data provide an initial framework for future studies and discussion of dose constraints. Selected dose-fractionation regimens may result in a satisfactory therapeutic ratio even after two previous courses of radiotherapy, if these were well tolerated.

A man in his 50s with neurological symptoms during cancer treatment. / En mann i 50-årene med nevrologiske symptomer under kreftbehandling.

Posterior reversible encephalopathy syndrome (PRES) is a rare clinicoradiographic disorder characterized by acute neurological symptoms with typical neuroimaging findings of vasogenic edema in posterior regions of the brain. This complication is linked to a number of medical conditions, and is increasingly being documented as a side effect associated with a number of therapeutic agents. We present a case of PRES as a result of treatment with the vascular endothelial growth factor (VEGF) multikinase inhibitor, regorafenib. A man in his 50's with known metastatic colorectal cancer presented with headache, vomiting, altered mental state, reduced hand coordination and dexterity, and a homonymous inferior quadrantanopia. Symptoms developed soon after completion of the 3rd regorafenib therapy cycle. Cerebral MRI demonstrated signs indicative of PRES with bilateral vasogenic edema in the occipitotemporal regions. Regorafenib was subsequently discontinued and the patient's condition improved gradually, with normalization of his neurological symptoms within a month. Albeit rare, PRES has been linked to VEGF treatments, particularly sorafenib, sunitinib and pazopanib, however this is the second reported case linking regorafenib with PRES. PRES is usually associated with good prognosis. However, delayed diagnosis and treatment may lead to permanent neurological symptoms, higher morbidity and in rare cases mortality. Therefore increased awareness of this condition is vital.