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Aim: The aim of this study was to evaluate the feasibility and efficacy, in terms of overall survival, of sequential systemic therapy in patients with metastatic castration-resistant prostate cance...

The winter darkness or polar night induces endocrine and metabolic mechanisms, which might reduce the efficacy of cancer treatment and thus contribute to shorter survival. Moreover, season-and weather-related treatment delays and irregularities might also cause reduced efficacy of anti-cancer drugs. Therefore, this study evaluated the prognostic impact of timing of chemotherapy (start during winter darkness or outside of this season), in terms of overall survival, in patients with metastatic castration-resistant prostate cancer (MCRPC) who received oncology care at the Nordland hospital Bodø. The study included 111 patients treated with first-line docetaxel chemotherapy for MCRPC. Twenty patients (18%) started their treatment during winter darkness (arbitrarily defined as ±4 weeks around 21 December). In unadjusted univariate analysis, survival was shorter in this group (median 10.2 vs. 18.9 months, p = 0.055). However, not all baseline parameters were equally distributed between the two groups. In multivariable-adjusted Cox regression analysis accounting for several confounding variables, only one factor was statistically significant: pre-chemotherapy serum lactate dehydrogenase level (a surrogate marker of disease burden). Thus, the present results suggest that seasonal variation is not a major contributor to the diverging survival outcomes observed after docetaxel chemotherapy.

Source at https://doi.org/10.1080/22423982.2019.1620086. The goal of the Norwegian Ministry of Health and Care Services is to offer an equal health-care service with the same outcomes wherever people are living within the country. The aim of this study was to evaluate whether this was true for patients diagnosed with metastatic prostate cancer (mPC) and living in Nordland County, a region with a challenging geography and climate and having, several small and remote communities and only 1 department of oncology. The latter is located in the main city, Bodø. We also compared a subgroup living in communities having lower average annual income (less than NOK 240,000 (equivalent to USD 28,600)) with patients living in Bodø (NOK 285,000 (USD 33,900)). Overall 288 patients were included and stratified into 3 subgroups (favourable distance and income, unfavourable distance and income, and unfavourable distance and favourable income). No statistically significant differences were observed regarding patient characteristics. There was no indication towards under-treatment among patients from the distant regions or the lower income region. Given that disparities were not observed, it was not surprising to see comparable survival outcomes (p=0.35). In conclusion, these results suggest that the health-care system in Nordland County successfully delivers state-of-the-art oncology care to patients with mPC.

Oncologists commonly overestimate the survival time of patients receiving palliative therapy, which may result in the administration of treatments that are too aggressive for patients near the end of their lives. Previous studies have discussed the negative implications of palliative radiotherapy if administered during the last month of life. Models predicting a limited survival time may improve the ability of the oncologists to tailor the treatment according to the needs of each individual patient. In the present study, prognostic factors for survival time, and the use of palliative radiotherapy during the last month of life, were analyzed in 873 patients. Models predicting the likelihood of administering such therapy were examined, and the risk of receiving radiotherapy during the last month of life was observed to be lower in patients with non-metastatic cancer than in those with metastatic cancer (7 vs. 13%, respectively; P=0.12). On multivariate analysis, 11 factors that significantly influenced the survival time were identified. These findings emphasize the complexity of potential prediction models. The most important risk factor regarding the prediction of extremely short survival times was observed to be an Eastern Cooperative Oncology Group performance status (ECOG PS) of 4, followed by an ECOG PS of 3 (median survival times, 14 and 64 days, respectively). A limited number of patients who received palliative radiotherapy during their last month of life died unexpectedly. Disease-specific prediction models were developed; however, the small number of events available for analysis limited their immediate clinical impact. Furthermore, these prediction models identified a minority of patients who received radiotherapy during the last month of life. In conclusion, the majority of the palliative radiotherapy courses administered to patients with advanced cancer during their last month of life may be preventable if accurate decision models for the clinic are developed. However, due to the complexity associated with the prediction of survival times in patients receiving palliative radiotherapy, large databases are required to allow accurate models to be established. The present study also discusses the recommendations of the Department of Oncology and Palliative Medicine of Nordland Hospital (Bodø, Nordland, Norway) with regard to the use of palliative radiotherapy during the last month of life of patients with terminal cancer.

Purpose To analyze indications for early palliative radiation therapy (RT) (ie, start within 1 month from cancer diagnosis), regimens used in clinical practice, rate of treatment completion and treatment in the last 30 days of life, and overall survival. Methods and materials Retrospective uni- and multivariate analyses covering a 4.5-year inclusion period. Results Seventeen percent of all palliative RT courses were administered in the specified time frame (n = 100 patients, 30 Gy in 10 fractions in 49%). Common indications were bone and brain metastases, whereas metastatic spinal cord compression or other emergencies comprised a minority. Only 14% of patients had no distant metastases. Most patients had non-small cell lung cancer (51%), whereas other high-incidence primary tumors such as breast, prostate, and colorectal cancer combined comprised 10%. Failure to complete RT occurred in 6%. Median survival was 3.6 months. A startling high rate of RT in the last 30 days of life was observed (19%). Risk correlated significantly with performance status and extent of metastatic disease. Conclusions The study population of patients who received early palliative RT is not identical to the general population described in previous studies, which covered the entire disease trajectory. Median survival was relatively short and rate of RT in the last 30 days of life higher than expected. Need for early palliative RT might be caused by large symptom burden and/or contraindication(s) for other management options, and might in many cases also be associated with adverse prognostic features and aggressive disease.

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.

Aims To explore the role of expanded assessment of metastatic extracranial organ involvement, as well as albumin and lactate dehydrogenase (LDH), i.e. surrogates of disease extent, in survival prediction models for patients with brain metastases. Materials and methods A retrospective analysis of 189 patients treated with whole brain radiotherapy was carried out. Uni- and multivariate analyses included recursive partitioning analysis classes, basic score for brain metastases and diagnosis-specific graded prognostic assessment (DS-GPA). Results Elevated LDH correlated significantly with extracranial organ involvement, low albumin with primary tumour type and primary tumour control. Elevated LDH, low albumin and a combination of both correlated significantly with overall survival. LDH, albumin and the number of extracranial organs involved (none, one, two or more harbouring metastases) were independent prognostic factors in multivariate analyses (if added to the three established scores mentioned above and also if added to individual parameters such as age, performance status, etc.). A combination of these three new prognostic factors predicted very short survival (median 0.7 months if all three were present). Conclusion We have previously defined patient groups in whom foregoing radiotherapy was unlikely to compromise survival. These were patients with a DS-GPA score of 0–1.5 points and age ≥75 years or Karnofsky performance status ≤50 or uncontrolled primary tumour with extracranial metastases to at least two organs. Patients with a combination of three new adverse features (elevated LDH plus low albumin plus extracranial metastases to at least two organs) might also be considered for best supportive care. Furthermore, it appears warranted to study whether scores such as DS-GPA can be optimised by integrating information on these three parameters.

Purpose. Validation of a Canadian three-tiered prognostic model (survival prediction score, SPS) in Norwegian cancer patients referred for palliative radiotherapy (PRT), and evaluation of age-dependent performance of the model. Patients and Methods. We analyzed all 579 PRT courses administered at a dedicated PRT facility between 20.06.07 and 31.12.2009. SPS was assigned as originally described, That is, by taking into consideration three variables: primary cancer type, site of metastases, and performance status. Results. Patients with poor prognosis (non-breast cancer, metastases other than bone, and Karnofsky performance status (KPS) ≤ 60) had median survival of 13 weeks. Those with intermediate prognosis (two of these parameters) survived for a median of 29 weeks, and patients with good prognosis for a median of 114 weeks, P<0.001. While this model performed well in patients who were 60 years or older, it was less satisfactory in younger patients (no significant difference between the good and intermediate prognosis groups). Conclusion. SPS should mainly be used to predict survival of elderly cancer patients. However, even in this group accuracy is limited because the good prognosis group contained patients with short survival, while the poor prognosis group contained long-term survivors. Thus, improved models should be developed.

This study aimed to develop a survival prediction model that might aid decision making when choosing between best supportive care (BSC) and brain radiotherapy (RT) for patients with brain metastases and limited survival expectation.A retrospective analysis of 124 patients treated with BSC, whole brain radiotherapy (WBRT), or radiosurgery was conducted. All patients had adverse prognostic features defined as 0-1.5 points according to the diagnosis-specific graded prognostic assessment score (DS-GPA) or GPA if primary tumor type was not among those represented in DS-GPA. Kaplan-Meier survival curves were compared between patients treated with BSC or RT in different scenarios, reflecting more or less rigorous definitions of poor prognosis. If survival was indistinguishable and this result could be confirmed in multivariate analysis, BSC was considered appropriate.Irrespective of point sum examined, DS-GPA by itself was not a satisfactory selection parameter. However, we defined a subgroup of 63 patients (51 %) with short survival irrespective of management approach (only 5 % of irradiated patients survived beyond 6 months; they had newly diagnosed, treatment-naïve lung cancer), i.e., patients in whom foregoing RT was unlikely to compromise survival. These were patients with 0-1.5 points and aged ≥ 75 years, had Karnofsky performance status ≤ 50, or had uncontrolled primary tumor with extracranial metastases to at least two organs.BSC is a reasonable choice in patients with limited life expectancy. After successful external validation of the selection criteria developed in this analysis, identification of patients who are unlikely to benefit from WBRT might be improved.

Objective To evaluate disease pattern, patient characteristics, and survival in patients treated for brain metastases from renal cell carcinoma. Methods Retrospective analysis of all patients with brain metastases from renal cell carcinoma treated between 1983 and 2009 in northern Norway. Results The time interval between first cancer diagnosis and brain metastases was dependent on initial TNM stage (median 42 months in stage II vs. 10 months in both stage III and stage IV). Only few patients did not harbor extracranial metastases. Systemic therapy after diagnosis of brain metastases has been used in only three patients. Surgical resection and/or radiosurgery have been administered in 34% of patients, but whole-brain radiotherapy (WBRT) alone remained the cornerstone. Median survival was 4.1 months (3.7 months in the WBRT alone group, 10.1 months in the surgery and/or radiosurgery group). Two factors were significantly associated with better survival: solitary brain metastasis and age ≤64 years. The prognostic impact of the recursive partitioning analysis classes was not confirmed, while the new graded prognostic assessment index performed better. Conclusions Surgical resection and/or radiosurgery contribute to prolonged survival. As most patients harbor extracranial metastases that threaten their lives, systemic treatment theoretically might play a role in the management of these patients, but more data need to be collected to confirm the clinical impact of immunotherapy, angiogenesis inhibition, and other signal transduction inhibitor approaches.

Recent studies from Italy, Japan and Norway have confirmed previous reports, which found that a large variety of palliative radiotherapy regimens are used for painful bone metastases. Routine use of single fraction treatment might or might not be the preferred institutional approach. It is not entirely clear why inter-physician and inter-institution differences continue to persist despite numerous randomized trials, meta-analyses and guidelines, which recommend against more costly and inconvenient multi-fraction regimens delivering total doses of 30 Gy or more in a large number of clinical scenarios. In the present mini-review we discuss the questions of whether doctors are ignoring evidence-based medicine or whether we need additional studies targeting specifically those patient populations where recent surveys identified inconsistent treatment recommendations, e.g. because of challenging disease extent. We identify open questions and provide research suggestions, which might contribute to making radiation oncology practitioners more confident in selecting the right treatment for the right patient.

Research activity related to different aspects of prevention, prediction, diagnosis and treatment of brain metastases has increased during recent years. One of the major databases (Scopus) contains 942 scientific articles that were published during the 5-year time period 2006–2010. Of these, 195 (21%) reported on single patient cases and 12 (1%) were reports of 2 cases. Little is known about their influence on advancement of the field or scientific merits. Do brain metastases case reports attract attention and provide stimuli for further research or do they go largely unrecognized? Different measures of impact, visibility and quality of published research are available, each with its own pros and cons. For the present evaluation, article citation rate was chosen. The median number of citations overall and stratified by year of publication was 0, except for the year 2006 when it was 2. As compared to other articles, case reports remained more often without citation (p

Objective: In spite of the large number of patients and increasing financial pressure on health care budgets worldwide, limited data on resource utilization after diagnosis of brain metastases are available. Methods: Prospective data were collected on all patients diagnosed with brain metastases during a time period of 2 years (n = 53). Treatment was best supportive care (BSC), primary radiotherapy (RT) and/or surgical resection. Eighty-five percent of patients had active extracranial disease. Costs were calculated from the hospital and nursing home’s point of view. Results: Overall, 11,532 patient days were analyzed. Treatment per patient amounted to 0.8 courses of whole-brain RT, 0.2 neurosurgical procedures, 0.1 radiosurgical procedures and 1.3 cycles of chemotherapy. Median survival in the BSC, RT and neurosurgery groups was 1.4, 4.6 and 11.0 months, respectively. Chemotherapy was associated with longer median survival. Four percent of the remaining lifetime was spent in nursing homes and 8% within hospitals. Forty-three percent of all hospital days and 47% of deaths were related to non-neurologic causes. The total cost per patient was 24,649 EUR (34,841 USD) and the corresponding cost per life year was 43,955 EUR (62,130 USD). Hospital care was the main cost factor. Conclusions: A considerable amount of resources is utilized in this patient group. Better tools for avoiding overtreatment and selecting patients for appropriate therapy are needed to achieve maximum value for money.

Treatment of non-small cell lung cancer (NSCLC) is challenging in many ways. One of the problems is disappointing local control rates in larger volume disease. Moreover, the likelihood of both nodal and distant spread increases with primary tumour (T-) stage. Many patients are elderly and have considerable comorbidity. Therefore, aggressive combined modality treatment might be contraindicated or poorly tolerated. In many cases with larger tumour volume, sufficiently high radiation doses can not be administered because the tolerance of surrounding normal tissues must be respected. Under such circumstances, simultaneous administration of radiosensitizing agents, which increase tumour cell kill, might improve the therapeutic ratio. If such agents have a favourable toxicity profile, even elderly patients might tolerate concomitant treatment. Based on sound preclinical evidence, several relatively small studies have examined radiotherapy (RT) with cetuximab in stage III NSCLC. Three different strategies were pursued: 1) RT plus cetuximab (2 studies), 2) induction chemotherapy followed by RT plus cetuximab (2 studies) and 3) concomitant RT and chemotherapy plus cetuximab (2 studies). Radiation doses were limited to 60-70 Gy. As a result of study design, in particular lack of randomised comparison between cetuximab and no cetuximab, the efficacy results are difficult to interpret. However, strategy 1) and 3) appear more promising than induction chemotherapy followed by RT and cetuximab. Toxicity and adverse events were more common when concomitant chemotherapy was given. Nevertheless, combined treatment appears feasible. The role of consolidation cetuximab after RT is uncertain. A large randomised phase III study of combined RT, chemotherapy and cetuximab has been initiated.

A case of leptomeningeal carcinomatosis in a patient with known brain and lung metastases from renal cell cancer without previous systemic therapy is presented. Neoplastic meningitis (NM) developed 31 months after first diagnosis of simultaneous extra- and intracranial recurrence of kidney cancer and surgical resection of a cerebellar metastasis. In spite of local radiotherapy to the macroscopic NM lesions in the cervical and lumbar spine followed by initiation of sunitinib, the patient succumbed to his disease 4 months after the diagnosis of NM. The untreated lung metastases progressed very slowly during almost 3 years of observation. This case illustrates important issues around both biological behaviour and treatment approaches in metastatic renal cell cancer.