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.

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.

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.

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.

Impact of the MDM2 splice-variants MDM2-A, MDM2-B and MDM2-C on cytotoxic stress response in breast cancer cells.

BACKGROUND: The murine double minute 2 (MDM2) is an oncogene and a negative regulator of the tumor suppressor protein p53. MDM2 is known to be amplified in numerous human cancers, and upregulation of MDM2 is considered to be an alternative mechanism of p53 inactivation. The presence of many splice variants of MDM2 has been observed in both normal tissues and malignant cells; however their impact and functional properties in response to chemotherapy treatment are not fully understood. Here, we investigate the biological effects of three widely expressed alternatively spliced variants of MDM2; MDM2-A, MDM2-B and MDM2-C, both in unstressed MCF-7 breast cancer cells and in cells subjected to chemotherapy. We assessed protein stability, subcellular localization and induction of downstream genes known to be regulated by the MDM2-network, as well as impact on cellular endpoints, such as apoptosis, cell cycle arrest and senescence. RESULTS: We found both the splice variants MDM2-B and -C, to have a much longer half-life than MDM2 full-length (FL) protein after chemotherapy treatment indicating that, under stressed conditions, the regulation of degradation of these two variants differs from that of MDM2-FL. Interestingly, we observed all three splice variants to deviate from MDM2-FL protein with respect to subcellular distribution. Furthermore, while MDM2-A and -B induced the expression of the pro-apoptotic gene PUMA, this effect did not manifest in an increased level of apoptosis. CONCLUSION: Although MDM2-B induced slight changes in the cell cycle profile, overall, we found the impact of the three MDM2 splice variants on potential cellular endpoints upon doxorubicin treatment to be limited.

Tumor marker analyses in patients with brain metastases: patterns of practice and implications for survival prediction research.

This study aims to explore patterns of practice of tumor marker analyses and potential prognostic impact of abnormal markers in patients with brain metastases from solid tumors. Previously, lactate dehydrogenase (LDH) and albumin were identified as relevant biomarkers. We performed a retrospective analysis of 120 patients with known LDH and albumin treated with whole-brain radiotherapy (WBRT) in two different situations: (1) brain metastases detected at initial cancer diagnosis (n = 46) and (2) brain metastases at later time points (n = 74, median interval 13 months). Twenty-six patients (57 %) from group 1 had at least one tumor marker analyzed, and 11 patients (24 %) had abnormal results. Twenty-two patients (30 %) from group 2 had at least one tumor marker analyzed, and 16 patients (22 %) had abnormal results. When assuming that LDH and albumin would be standard tests before WBRT, additional potential biomarkers were found in 36 % of patients with normal LDH and albumin. Marker positivity rates were for example 80 % for carcinoembryonic antigen (CEA) in colorectal cancer and 79 % for CA 15-3 in breast cancer. Abnormal markers were associated with presence of liver metastases. CA 15-3 values above median predicted shorter survival in patients with breast cancer (median 1.9 vs. 13.8 months, p = 0.1). Comparable trends were not observed for various markers in other tumor types. In conclusion, only a minority of patients had undergone tumor marker analyses. Final group sizes were too small to perform multivariate analyses or draw definitive conclusions. We hypothesize that CA 15-3 could be a promising biomarker that should be studied further.

Comprehensive Analysis of Blood Test Results Predicting Prognosis in Patients Undergoing Whole-brain Radiotherapy for Brain Metastases.

BACKGROUND/AIM: Blood tests, such as those included in the validated LabBM score (laboratory parameters in patients with brain metastases) predict survival after treatment of brain metastases. The model incorporates five test results [serum lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin, platelets and hemoglobin]. However, many other abnormalities, albeit less well-studied, may be present in patients with metastatic cancer. Therefore, this study aimed to examine a broader range of blood tests. PATIENTS AND METHODS: This retrospective analysis included 132 patients managed with primary whole-brain radiotherapy. Additional tests, such as liver enzymes, lymphopenia, hyponatremia, and others, were also conducted. Extracranial disease extent was also analyzed. RESULTS: According to forward conditional Cox regression analyses, blood tests (albumin, hemoglobin, lymphopenia, hyponatremia) in conjunction with the number of organs affected by extracranial metastases (at least two, such as liver and bones) provided the best prognostic model. Based on these parameters, at least four prognostic strata can be assigned (median survival between 4.6 and <1 months, p=0.0001). CONCLUSION: This initial pilot study in a limited number of patients suggests that numerous blood test results may contribute to further refinement of existing prognostic models, and provides justification for additional large-scale studies.

Return to Work After Breast Cancer Treatment: An Electronic Health Record-based Study in North Norway.

BACKGROUND/AIM: Breast cancer treatment may interfere with work ability. Previous return-to-work studies have often focused on participants who were invited to participate after treatment completion. Participation varied, resulting in potential selection bias. This is a health-record-based study evaluating data completeness, both at baseline and one year after diagnosis. Correlations between baseline variables and return to work were also analyzed. PATIENTS AND METHODS: This is a retrospective review of 150 relapse-free survivors treated in Nordland county between 2019 and 2022 (all-comers managed with different types of systemic treatment and surgery). Work status was assessed in the regional electronic patient record (EPR). A 65-years age cut-off was employed to define two subgroups. RESULTS: At diagnosis, occupational status was assessable in all 150 patients. Almost all patients older than 65 years of age were retired (79%) or on disability pension for previously diagnosed conditions (19%). Data completeness one year after diagnosis was imperfect, because the EPR did not contain required information in 19 survivors. The majority of those ≤65 years of age at diagnosis returned to work. Only 14 of 88 patients (16%) did not return to work. Postoperative nodal stage was the only significant predictive factor. Those with pN1-3 had a lower return rate (68%) than their counterparts with lower nodal stage. CONCLUSION: This pilot study highlights the utility and limitations of EPR-based research in a rural Norwegian setting, emphasizing the need for comprehensive, individualized interventions to support breast cancer survivors in returning to work. The findings underscore the importance of considering diverse sociodemographic and clinical factors, as well as the potential benefits of long-term, population-based studies to address these complex challenges.

The LabPS score: Inexpensive, Fast, and Site-agnostic Survival Prediction.

OBJECTIVES: To provide a widely applicable, blood-biomarker-based and performance-status-based prognostic model, which predicts the survival of patients undergoing palliative non-brain radiotherapy. This model has already been examined in a cohort of patients treated for brain metastases and performed well. METHODS: This was a retrospective single-institution analysis of 375 patients, managed with non-ablative radiotherapy to extracranial targets, such as bone, lung, or lymph nodes. Survival was stratified by LabPS score, a model including serum hemoglobin, platelets, albumin, C-reactive protein, lactate dehydrogenase, and performance status. Zero, 0.5, or 1 point was assigned and the final point sum calculated. A higher point sum indicates shorter survival. RESULTS: The LabPS score predicted overall survival very well (median 0.6 to 26.5 mo, 3-month rate 0% to 100%, 1-year rate 0% to 89%), P =0.0001. However, the group with the poorest prognosis (4.5 points) was very small. Most patients with comparably short survival or radiotherapy administered in the last month of life had a lower point sum. Additional prognostic factors, such as liver metastases, opioid analgesic use, and/or corticosteroid medication, were identified. CONCLUSIONS: If busy clinicians prefer a general prognostic model rather than a panel of separate diagnosis-specific/target-specific scores, they may consider validating the LabPS score in their own practice. In resource-constrained settings, inexpensive standard blood tests may be preferable over imaging-derived prognostic information. Just like other available scores, the LabPS cannot identify all patients with very short survival.

Independent Validation of a Risk Stratification Model Predicting Survival in Elderly Patients Irradiated for Bone Metastases.

BACKGROUND/AIM: Many patients with bone metastases receive palliative radiotherapy. However, treatment personalization tools are needed, due to heterogeneous survival. The aim of this study was to analyze the validity of the prognostic survival model, originally developed by Rades et al., because international variations in clinical practice and survival outcomes may impact on the performance of predictive tools. PATIENTS AND METHODS: Data from a single institution were retrospectively analyzed. The study included 305 patients managed with palliative radiotherapy for bone metastases. The Rades et al. score was assigned and the resulting 3 prognostic strata were compared. RESULTS: The median overall survival for the 3 strata was 48, 248, and 1065 days, respectively (p<0.001). However, the original break-down (17 points versus 18-25 points versus >25 points) was not in accordance with the overlapping survival curves in some of the subgroups, leading us to propose slight adjustments. The modified model also performed satisfactorily in older patients (age ≥80 years; median survival 26, 192 and 489 days, respectively, p<0.001). CONCLUSION: The original Rades et al. survival score was a valid prognostic model in our Norwegian validation database. However, inclusion of patients with 18 points into the poor prognosis group is suggested as a modification to enhance the score's performance.

Independent Validation of a Unifying Prognostic Model for Intracranial and Extracranial Metastasis-directed Radiotherapy.

BACKGROUND/AIM: The aim of this study was to analyze the validity of a unifying prognostic model, originally developed by Kowalchuk et al., because relevant variations in clinical practice and observed survival may impact on the performance of predictive tools. PATIENTS AND METHODS: Retrospectively, data from a single institution were analyzed. The study included 253 patients managed with radiotherapy for spine and/or brain metastases. The Kowalchuk et al. score [3 parameters including performance status, number of organ systems involved with disease outside of the organ system of the treatment target, and treatment of intracranial target(s)] was assigned and the resulting prognostic strata compared. RESULTS: The decision tool developed by Kowalchuk et al. performed well, e.g., in terms of 2-year survival. Complementary information could be obtained by analyses of blood test results such as hemoglobin, albumin, and C-reactive protein. CONCLUSION: The new unifying score emerged as a valid prognostic model in our external validation database.

Early death after palliative radiation treatment: 30-, 35- and 40-day mortality data and statistically robust predictors.

BACKGROUND: This study analyzed mortality after radiotherapy for bone metastases (287 courses). Endpoints such as treatment in the last month of life and death within 30, 35 and 40 days from start of radiotherapy were evaluated. METHODS: Different baseline parameters including but not limited to blood test results and patterns of metastases were assessed for association with early death. After univariate analyses, multi-nominal logistic regression was employed. RESULTS: Of 287 treatment courses, 42 (15%) took place in the last month of life. Mortality from start of radiotherapy was 13% (30-day), 15% (35-day) and 18% (40-day), respectively. We identified three significant predictors of 30-day mortality (performance status (≤ 50, 60-70, 80-100), weight loss of at least 10% within 6 months (yes/no), pleural effusion (present/absent)) and employed these to construct a predictive model with 5 strata and mortality rates of 0-75%. All predictors of 30-day mortality were also associated with both, 35- and 40-day mortality. CONCLUSION: Early death was not limited to the first 30 days after start of radiotherapy. For different cut-off points, similar predictive factors emerged. A model based on three robust predictors was developed.

Patterns of Care and Survival in Cancer Patients with Brain Metastases Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have become a mainstay of treatment for different cancer types. The purpose of this study was to evaluate patterns of care and overall survival (OS) after diagnosis of brain metastases in patients managed with ICI as component of care. METHODS: This was a retrospective cohort study. Fifty patients were included (34 with brain metastases at first cancer diagnosis, 16 with metachronous spread). RESULTS: Depending on symptoms, lesion number and size, and other individualized criteria, multidisciplinary tumor (MDT) board discussion resulted in highly individualized treatment sequences. Selected patients received systemic treatment alone. Twenty-four patients (48%) had any stereotactic radiosurgery or neurosurgical resection at some point in time (upfront/salvage). Only 7 patients (14%) were never treated with brain irradiation or neurosurgery. Median OS was 13.0 months. Better Karnofsky performance status, absence of extracranial metastases, and time interval between cancer diagnosis and brain metastases of 0-18 months predicted for improved survival. Treatment sequence was not associated with survival. Patients without extracranial metastases had median OS of 52.2 months. CONCLUSION: Long-term survival is possible in patients managed with ICI ± brain-directed treatment. This study did not identify a clear treatment sequence of choice. MDT assessment at diagnosis and each progression is recommended to ensure favorable outcomes.

A Case of Five-Year Survival After Combined-Modality Treatment for Non-Small Cell Lung Cancer With Intraspinal Metastasis.

This case report describes the treatment approach and outcome in a 69-year-old female patient with non-small cell lung cancer (NSCLC) diagnosed with T4 N2 M1b (intraspinal) disease. The two most common targets for tyrosine kinase inhibitors (epidermal growth factor receptor and anaplastic lymphoma kinase) were not expressed. Programmed death-ligand 1 (PD-L1) was expressed in <50% of the tumor cells. In 2016, initial guideline-concordant treatment with carboplatin/vinorelbine chemotherapy was initiated. Between the first two cycles, all positron emission tomography (PET) positive lesions were irradiated with 30 Gy in 10 fractions (lung, nodes, thoracic spinal manifestation). After nine months with excellent response (at least partial remission, possibly fibrosis only), bilateral lung metastases were diagnosed. The patient was started on nivolumab monotherapy (later atezolizumab due to a change in National practice) and completed two years of treatment. She is currently in continued complete remission with regular follow-up examinations. This case illustrates that outcomes comparable to those observed in patients with limited brain metastases may be observed in patients with localized intraspinal disease and that immune checkpoint inhibitors play an important role in the management of metastatic NSCLC.

Established Serum Biomarkers Are Prognostic Factors in Patients With Oligometastatic Cancer and Brain Involvement.

BACKGROUND/AIM: This study was designed to evaluate the prognostic impact of the previously validated LabBM score (serum lactate dehydrogenase, C-reactive protein, albumin, hemoglobin, platelets) in a new setting, namely patients with a limited number of brain metastases, arbitrarily defined as max. 4 brain lesions, from common tumor types such as lung and breast cancer. A total of 5 metastatic lesions overall were allowed to comply with current definitions of oligometastatic cancer. PATIENTS AND METHODS: For this retrospective single-institution analysis, 101 patients were identified from a previously described, prospectively maintained database. RESULTS: Twenty-one patients (21%) had extracranial metastases. Non-small cell and small cell lung cancer were the prevailing tumor types (78%). Forty-nine patients (49%) had normal blood test results (LabBM score 0 points). Their median survival (23 months) was significantly longer than that of patients with higher LabBM score. In multivariate analysis, LabBM score, performance status and single brain metastasis were associated with significantly better survival. Limited extracranial metastases did not impair prognosis. Patients with LabBM score 0 had a 5-year survival rate of 27% after surgery (n=24) and 39% after stereotactic radiotherapy (n=13), respectively (p=0.3). CONCLUSION: Blood biomarkers can be regarded as surrogate of the metastatic burden in the body, which is not always detectable by imaging methods. In contrast to circulating tumor cells and other emerging markers, the LabBM score is inexpensive. Patients with LabBM score >0 had a 2.8-fold increased risk of death. The score might be helpful in predicting survival improvement provided by ablative local treatment of oligometastases.

Shortened Palliative Radiotherapy Results in a Lower Rate of Treatment During the Last Month of Life.

Introduction Palliative radiotherapy (PRT) during the last month of life (PRT30) should be avoided because relevant clinical benefits are unlikely to occur. While traditional short-course fractionation regimens are suitable for most patients, a minority may derive gains from higher doses of PRT. Compared to older regimens such as 13 fractions of 3 Gy, more hypofractionated, non-ablative concepts with reduced overall treatment time are not well studied. Methods Retrospective analysis (2017-2020) of 107 patients treated to metastatic lesions (one or two target volumes per patient) with traditional >2 weeks regimens or newer ≤2 weeks regimens, e.g. seven fractions of 5 Gy or five fractions of 6 Gy. Results Failure to complete radiotherapy was registered in 8% of patients (traditional fractionation) and 1%, respectively (p=0.12). Moderate rates of PRT30 were observed (11% and 6%, respectively, p=0.44). PRT30 was more likely in patients irradiated for brain or lymph node metastases. Utilization of newer ≤2 weeks regimens was highest in 2020, presumably as a result of the coronavirus disease 2019 (COVID-19) pandemic. Conclusion The implementation of newer fractionation regimens for selected patients has resulted in acceptable rates of non-completion and PRT30. Optimal selection criteria remain to be determined. Established, guideline-endorsed short-course regimens such as five fractions of 4 Gy and 8-Gy single fractions continue to represent important PRT approaches.

Dual Use of the METSSS Model Predicting Survival After Palliative Radiotherapy: An Exploratory Analysis.

INTRODUCTION: The recently published METSSS model, which was developed for prediction of survival after palliative radiotherapy, includes age, sex, cancer type, localization of distant metastases, Charlson-Deyo comorbidity score and radiotherapy site. Its ability to predict other relevant endpoints has not been studied yet. Therefore, this exploratory study analyzed the endpoints "unplanned termination of radiotherapy" and "treatment in the last 30 days of life" in the METSSS-defined risk groups (low/medium/high). METHODS: The risk group was assigned in the METSSS online calculator for our patient cohort with non-hematological malignancies treated between 2009 and 2014 during the first course of treatment (resembling details of the original METSSS study). All patients were treated with classical palliative dose/fractionation regimes such as five fractions of 4 Gy, 10 fractions of 3 Gy or 13 fractions of 3 Gy. No stereotactic high-dose radiation was utilized. Given that single-fraction radiotherapy cannot be discontinued, patients treated with 8 Gy x1 for uncomplicated painful bone metastases were excluded. Both completed and discontinued multi-fraction radiotherapy courses (at least two fractions intended) were included. RESULTS: The study included 290 patients, 19 of whom failed to complete their prescribed course of palliative radiotherapy (7%). Thirty-nine (13%) were irradiated in the last 30 days of life. Only one patient was classified as low-risk according to the METSSS model (medium: 15, high: 274). Only Eastern Cooperative Oncology Group (ECOG) performance status (PS) was significantly associated with incomplete treatment. All 16 patients with low/medium METSSS risk scores completed their prescribed course of radiotherapy, compared to the 93% completion rate in the high-risk group, p=0.41. With regard to treatment in the last 30 days of life, ECOG PS, metastases to brain, liver and lung, and the number of prescribed fractions were statistically significant. One patient with a low/medium METSSS risk score was treated in the last 30 days of life (6%), compared to 14% in the high-risk group, p=0.49. CONCLUSION:  Unexpected imbalances in the METSSS risk group size resulted in lower statistical power than anticipated. Patients with low/medium METSSS risk scores performed numerically better. However, other predictive factors, especially ECOG PS, which is not part of the METSSS model, maybe more relevant. Further efforts towards the application of the model beyond its original objective cannot be recommended.

Implementation of Locoregional Adjuvant Radiotherapy for Breast Cancer in a Rural Healthcare Region: Toxicity Outcomes in the Initial Cohort.

BACKGROUND/AIM: The aim of this study was to analyze the toxicity of locoregional adjuvant breast cancer radiotherapy after implementation of this service in a rural healthcare region with long travel distance. PATIENTS AND METHODS: This was a retrospective single-institution analysis of 87 consecutive female patients (the initial cohort), managed with conventionally fractionated 3-D conformal radiotherapy with or without boost, including both post mastectomy and breast conservation scenarios. Treatment was administered in line with comprehensive national guidelines. Intensity-modulated techniques were not utilized. RESULTS: The median follow-up time was 4 years. None of the patients developed any grade IV side-effects. According to Radiation Therapy Oncology Group criteria, acute grade 2b or 3 skin toxicity was observed in 16%. In addition, 35% developed acute grade 2a skin reactions. A trend was observed regarding grade 2-3 skin toxicities and administration of a boost (p=0.058). There was a significant association between the clinical target volume of the breast and grade 2-3 skin reactions in women who had breast-conserving surgery (p=0.016). Five patients (6%) developed grade 1 pneumonitis, unrelated to dosimetric or other baseline parameters. CONCLUSION: The toxicity profile after a median follow-up of 4 years was in accordance with published data. Recently, intensity-modulated techniques have been implemented at the study center, which may reduce radiotherapy toxicity in patients with large clinical target volume due to better dose homogeneity.

Independent External Validation of the METSSS Model Predicting Survival After Palliative Radiotherapy.

BACKGROUND/AIM: A validation of the recently published METSSS model (developed from a large US database) predicting survival after palliative radiotherapy was performed. METSSS includes age, sex, cancer type, localization of distant metastases, comorbidity, and radiotherapy site. PATIENTS AND METHODS: Both 1- and 5-year survival was assessed in the validation cohort. Deviations between model-predicted and observed survival were analyzed. RESULTS: The METSSS model predicted a 1-year survival of 29% (cohort median, predicted probability 0-74% in individual patients). The observed 1-year survival rate was 33% (median survival 5.3 months). The corresponding figures for predicted 5-year survival were 0% and 0-46% (observed rate 3%). Statistical comparison of the survival curves was possible for two of three strata (insufficient number of low-risk patients) and the resulting p-value was 0.045. CONCLUSION: A complete validation was hampered by imbalances in group size. More than 90% of our patients were classified as high risk. If this distribution is representative for other countries, the METSSS model might need adjustment. However, its general ability to predict survival appears promising.

30-day mortality in patients treated for brain metastases: extracranial causes dominate.

BACKGROUND: Established prognostic models, such as the diagnosis-specific graded prognostic assessment, were not designed to specifically address very short survival. Therefore, a brain metastases-specific 30-day mortality model may be relevant. We hypothesized that in-depth evaluation of a carefully defined cohort with short survival, arbitrarily defined as a maximum of 3 months, may provide signals and insights, which facilitate the development of a 30-day mortality model. METHODS: Retrospective analysis (2011-2021) of patients treated for brain metastases with different approaches. Risk factors for 30-day mortality from radiosurgery or other primary treatment were evaluated. RESULTS: The cause of death was unrelated to brain metastases in 61%. Treatment-related death (grade 5 toxicity) did not occur. Completely unexpected death was not observed, e.g. accident, suicide or sudden cardiac death. Logistic regression analysis showed 9 factors associated with 30-day mortality (each assigned 3-6 points) and a point sum was calculated for each patient. The point sum ranged from 0 (no risk factors for death within 30 days present) to 30. The results can be grouped into 3 or 4 risk categories. Eighty-three percent of patients in the highest risk group (> 16 points) died within 30 days, and none survived for more than 2 months. However, many cases of 30-day mortality (more than half) occurred in intermediate risk categories. CONCLUSION: Extracranial tumor progression was the prevailing cause of 30-day mortality and few, if any deaths could be considered relatively unexpected when looking at the complete oncological picture. We were able to develop a multifactorial prediction model. However, the model's performance was not fully satisfactory and it is not routinely applicable at this point in time, because external validation is needed to confirm our hypothesis-generating findings.