The Impact of Sidedness on the Efficacy of Anti-EGFR-Based First-Line Chemotherapy in Advanced Colorectal Cancer Patients in Real-Life Setting-A Nation-Wide Retrospective Analysis (RACER).

Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, p = 0.010), and median depth of response: -36.7% vs. -50.0% (p = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics.

Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study.

BACKGROUND: Oxaliplatin-based therapy with FOLFOX-4 or CAPOX administered over 6 months remains the standard adjuvant treatment for stage III colon cancer (CC) patients. However, many patients experience dose reduction or early termination of chemotherapy due to oxaliplatin toxicity, which may increase the risk of early recurrence. The objective of this study was to analyze the relationship between the relative dose intensity of oxaliplatin (RDI-O) and early recurrence among stage III CC patients. METHODS: The study included 365 patients treated at five oncology centers in Poland between 2000 and 2014. Survival analysis was performed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazard model; multivariate analysis was performed with the stepwise forward approach. For all analyses the α level of 0.05 was employed. RESULTS: The median follow-up was 51.8 months (range 8.2-115.1). Early recurrence < 36 months after surgery occurred in 130 patients (37.8%). In this group 51 (39.2%) and 87 (66.9%) of patients were low and high-risk, respectively. Receipt < 60% of RDI-O was associated with early recurrence within 18 months after surgery (OR = 2.05; 95%CI: 1.18-3.51; p = 0.010), especially in low-risk group (HR = 1.56 (95%CI: 0.96-2.53), p = 0.07). In the multivariate analysis early recurrence was correlated with grade (OR = 2.47; 95% CI: 1.25-4.8; p = 0.008), pN (OR = 2.63; 95% CI: 1.55-4.54; p < 0.001), the number of lymph nodes harvested (OR = 0.51; 95% CI: 0.29-0.86; p = 0.013) and RDI-O (OR = 1.91; 95%CI: 1.06-3.39; p = 0.028). The early vs. late recurrence negatively correlated with OS regardless of the RDI-O (HR = 22.9 (95%CI: 13.9-37.6; p < 0.001). CONCLUSIONS: RDI-O < 60% in adjuvant therapy among stage III CC (especially in low-risk group) increases the risk of early recurrence within 18 months of surgery. Patients with early recurrence showed worse overall survival regardless of the RDI-O.

Quality of life during chemotherapy, hormonotherapy or antiHER2 therapy of patients with advanced, metastatic breast cancer in clinical practice.

INTRODUCTION: Breast cancer is one of the most important health problems in the world. In recent years, this cancer has achieved a reduction in mortality, which is attributed to the introduction of mass screening and greater efficacy of post-operative treatment. Many patients with breast cancer have indications only for palliative therapy, but the impact of these methods on the quality of life of patients remains a subject of controversy. It remains unknown whether the progress in improving the quality of life in clinical trials also applies to patients treated as part of daily clinical practice. Data on the results of the impact of conducted therapies on the quality of life outside of clinical trials are scarce. METHODS: The results of palliative chemotherapy and first-line hormonotherapy in 351 patients with advanced, metastatic breast cancer treated in the period from January 2010 to December 2016 in two centres were analysed. RESULTS: The average age of patients was 62 ± 9.8 years; 139 patients received chemotherapy, 91 - therapy containing trastuzumab, and 121 - hormone therapy. A partial response was obtained in 111 patients (32%), stabilization in 150 (43%), and in 90 patients (26%) progression. Median survival time in the whole group of patients was 36 months. Chemotherapy compared to trastuzumab and hormonotherapy was associated with greater total toxicity (p = 0.03). There was a significant relationship between the type of therapy (hormonotherapy, chemotherapy, targeted therapy) and the general average quality of women's life measured with the EORC-QLQ-C30 questionnaire. In addition, a statistically significant difference was found in some somatic complaints (the scale of QLQ-BR23 symptoms) depending on the type of therapy performed. The lowest intensity of complaints was reported by patients during hormonotherapy, then during targeted therapy, and the largest during chemotherapy. CONCLUSIONS: There is no effect of chemotherapy on the overall quality of life. Hormone therapy and trastuzumab therapy improved the quality of life of the treated patients in clinical practice.

Prognostic Value of Patient Knowledge of Cancer on Quality of Life in Advanced Lung Cancer During Chemotherapy.

The purpose of the study was to assess the impact of cancer knowledge and patient's lifestyle on QOL and the relationship between QOL and various environmental factors in patients with non-small-cell lung cancer treated with chemotherapy. The study group consisted of 129 patients with metastatic lung cancer patients treated between May 2010 and December 2015 in two centres. The knowledge of cancer and their lifestyle was rated by method of diagnostic survey, using the Behavioral Health Inventory IZZ by Prof. Juczynski. We sought factors affecting to response to treatment, overall survival and quality of life. The general level of knowledge of cancer and the level of health behaviours was low. Ninety percent of lung cancer patients were smokers. The average age of the study group was 64 years. Eighty-nine patients received chemotherapy with cisplatin, 28 schemes containing carboplatin, 6 inhibitors of EGFR tyrosine kinase, and 6 vinorelbine or gemcitabine monotherapy. Complete regression was observed in 2 patients, partial response in 33 patients (26%), stable disease in 51 (40%) and 54 (42%) patients had progression. In multivariate analysis, significant effects on survival were performance status, schemes of treatment and response to treatment. Quality of life before and after treatment did not differ from each other. We found impact on quality of life: performance status, response to treatment and knowledge of cancer and lifestyle. The level of knowledge of oncological patients and their lifestyle observed in clinical practice are associated with QOL.

Prognostic Value of Knowledge of Cancer and Used Unconventional Therapy Methods on Quality of Life in Advanced, Metastatic Colorectal Cancer in Clinical Practice.

Colorectal cancer (CRC) is the third most common malignancy in the world and the second cause of cancer-related deaths. Despite the search for new therapeutic agents, there are still many doubts concerning the quality of life (QOL) improvement in palliative patients. In this study, we assessed the impact of oncology knowledge on QOL and the relationship between QOL and various environmental factors and unconventional treatment methods in patients with CRC treated with chemotherapy and targeted therapy. The results of first-line palliative chemotherapy in 330 patients with colorectal cancer treated between January 2010 and December 2016 in two centers were analyzed. The average age of patients was 66 ± 11.7 years. Median survival time was 25 months. In multivariate analysis, the performance status and response to treatment had a significant effect on survival time. A trend towards shorter survival was also observed in patients receiving 5-FU monotherapy, in elderly patients and in patients with less oncology knowledge. A relationship between general quality of life and performance status (PS 0 vs. PS > 0), response to treatment and oncology knowledge was found. Patients with limited oncology knowledge more often used unconventional therapy methods in parallel with the treatment. In patients over 70 years of age and in patients with worse overall condition, 5-FU monotherapy was more commonly used (p < 0.01). The level of oncology knowledge of the treated patients observed in everyday clinical practice may be related to some parameters of treatment effectiveness assessment, such as QOL and may be related to the use of unconventional treatment methods. Those, in turn may have an impact on the QOL of the treated patients.

Hodgkin lymphoma of the elderly patients: a retrospective multicenter analysis from the Polish Lymphoma Research Group.

We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1-190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63-0.85) and 0.90 (95%CI: 0.82-0.98) for ES; 0.51 (95%CI: 0.44-0.57), and 0.81 (95%CI: 0.75-0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG <2 and age >70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG< 2, age >70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.

Evaluation of the Impact of Cancer Treatment on the Adoption and Consolidation of Pro-Health Attitudes in the Field of Cancer in Treated Patients with Colon Cancer.

Colorectal cancer is the second most common cause of cancer deaths worldwide. Although progress in the development of new drugs over the last two decades has expanded treatment options for this disease, many significant problems relating to their optimization remain to be solved. Data on the cancer knowledge and the healthy behavior and lifestyle in patients with colorectal cancer in Poland is missing. We analyzed the course and results of treatment of first-line chemotherapy in 165 patients diagnosed with colorectal cancer treated between May 2010 and December 2013. The respondent's knowledge in the field of cancer and their lifestyle before and after the treatment were rated. The results were compared with a control group. Mean age was 60.89 ± 8.69 years, median 59 years. The general knowledge about cancer and the level of healthy lifestyle before treatment were low. After treatment, both the knowledge about cancer and the level of healthy lifestyle increased compared to the control group. There was a clear relationship between the level of knowledge about cancer and the willingness to adopt attitudes and healthy behavior by patients. In our analysis, the overall quality of life in patients treated with first-line palliative chemotherapy of colorectal cancer did not change during treatment. Our results indicate the need to implement an educational program on cancer prevention in treated patients, and the analysis of quality of life and other factors than treatment effect remains controversial.

Assessment of quality of life in advanced, metastatic prostate cancer: an overview of randomized phase III trials.

INTRODUCTION: The chief therapeutic goal in metastatic prostate cancer is prolongation of survival with good quality of life . Quality of life (health-related) is often used as an endpoint parameter in phase III trials in metastatic prostate cancer, but the value of using HRQOL in this context has not been assessed to date. METHODS: In order to evaluate the role of HRQOL assessment in contemporary phase III trials in prostate cancer, we searched the PubMed database to identify publications presenting the results of these trials on systemic therapies for prostate cancer published between January 2000 and December 2015. The analysis was separately presented in ten leading journals. We searched for companion papers reporting on QOL separately. RESULTS: We identified 84 studies which included a total of 57,193 patients in ten leading journals and 27 studies (7270 patients) in other journals. HRQOL parameters were described or mentioned in the main publication in 25 publications and four companions in total. There was no obvious trend in quality of life reported over two 8-year periods . The explicit statistical comparisons were reported in 22/25 cases (88 %), with significant difference in only 10/25 (40 %) studies and in eight cases (80 %) was conducive to the examined arm. There was no significant association between improvements in HRQOL and improvements in overall survival (OS) or any other primary endpoint in the analyzed studies. Only one study was found which presented the difference in quality of life with no difference in the primary endpoint. CONCLUSIONS: HRQOL is an indicator of benefit during treatment of patients with metastatic prostate cancer, but it is unlikely that HRQOL results can help clinicians choose between treatments given that they are not correlated with changes in OS or at other primary endpoints.

Health-related quality of life assessment in contemporary phase III trials in advanced colorectal cancer.

BACKGROUND: Health-related quality of life (HRQOL) is often used as an endpoint in cancer clinical trials. We assessed the frequency and correlates of HRQOL use in phase III trials in advanced colorectal cancer. METHODS: We searched PubMed for phase III trials published between January 1998 and December 2014, as well as for companion papers reporting on HRQOL separately. We excluded papers reporting on correlative biology or prognostic factors in isolation from the main trial results, as well as trials on supportive care and on local therapy. RESULTS: We retrieved 111 trials that enrolled a total of 61,531 patients in 241 trial arms. HRQOL was reportedly used as an endpoint in 40 trials (36%), in all but two as a secondary endpoint. There was a significant decrease in the use of HRQOL, with frequencies of 46% in trials published between 1998 and 2006, and 27% between 2007 and 2014 (P=0.04). Trials with HRQOL as endpoint were significantly larger than trials without such endpoint. Formal statistical comparisons involving HRQOL parameters were reported in 36 of 40 trials (90%) with HRQOL assessment, with a significant difference between arms found in 14 (39%), six of which favoring the experimental arm. HRQOL gains were usually accompanied by improvements in efficacy endpoints, but were not related to the number of patients or chemotherapy line. CONCLUSIONS: HRQOL has been formally assessed in about one-third of recent phase III trials in advanced colorectal cancer, with a significant gain in HRQOL in about 40% of cases. It is questionable whether HRQOL results may largely help select between competing treatments. This assumption may be one of the reasons for the apparent decreased use of HRQOL as an endpoint in phase III trials in this disease.

PEG3 domain gene expression in maternal and foetal placenta in intrauterine growth restricted bovine foetuses.

We used a genetic (MIMT1(Del)) model of intrauterine growth restriction to investigate dysregulation of PEG3 domain gene expression in bovine foetal and maternal placenta. ZIM2, APEG3 and PEG3 expressions were similarly reduced in MIMT1(Del/) (WT) foetal placenta, suggesting coordinated regulation. Methylation of DNA CpG sites associated with these genes showed no differences, but differences in the levels of MIMT1 RNA methylation at three CpG sites were found in foetal placenta. Our data are consistent with the presence of a bidirectional promoter 5' of MIMT1 and suggest a regulatory role for the MIMT1 non-coding transcript. PEG3 domain expression on the maternal placenta side was not affected by the foetal mutation.

[Prognostic value of knowledge of cancer on quality of life in advanced colorectal cancer in clinical practice].

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignancy and the second cause of cancer deaths worldwide. The development of new drugs in recent years has improved the outcomes, but it still a lot of questions to improve the quality of life of patients receiving palliative care in daily clinical practice. In this study, we evaluated the impact of knowledge of cancer on QOL and the relationship between QOL and various environmental factors in patients with CRC treated with chemotherapy. MATERIAL AND METHODS: We analyzed the results of first-line palliative chemotherapy in 165 patients with colorectal cancer treated between May 2010 and December 2014 in two centers. 98 (59%) patients had earlier received postoperative chemotherapy, including 79 with the participation of oxaliplatin. The mean age of patients was 61 ± 8.7 years. RESULTS: The median survival time was 15 months. In multivariate analysis, significant effect on survival were performance status and response to treatment. There was also a trend toward shorter survival in patients treated with single 5-Fu chemotherapy, in elderly patients and in patients exhibiting a lower knowledge of oncology. We found relationship between overall quality of life and performance status (0 vs> 0), response to treatment and oncological knowledge. The chemotherapy with single chemotherapy 5-Fu was often used in patients over the age of 70 years and in patients with low performance status (p< 0.01). CONCLUSIONS: The level of knowledge of cancer observed in clinical practice may be related to certain parameters to evaluate the effectiveness of treatment, such as QOL.

[Assessment of knowledge in the field of cancer and selected health-promoting behaviors among patients with advanced colorectal cancer during chemotherapy].

Introduction: Neoplastic diseases are the second leading cause of death in developed countries. Colorectal cancer is the third most common malignancy and the second cause of cancer deaths worldwide. Lifestyle and related health behaviors have impact on health condition and course of treatment. Aim: Evaluation of oncological knowledge and health behaviors of patients with colorectal cancer in relation to social and demographic factors. Material and Methods: The study group consisted of 165 patients with colorectal cancer treated in the period from May 2010 to December 2014 in two centers. The mean age of patients was 61 ± 8.7 years. We rated knowledge of respondents in the field of cancer and health lifestyle with method of diagnostic survey, using the Behavioral Health Inventory by prof. Juczynski. Results: The general level of knowledge on cancer was low, and the level of severity of health behaviors was average. It has been proven the association between the state of knowledge concerning cancer and readiness to adopt attitudes and healthy behaviors by CRC patients. The level of health practices was significantly higher in people with higher education, in women and in people with a higher knowledge of oncology. Patients had lower levels of mental attitude and eating habits than the standardized value. Conclusions: The level of knowledge of patients with CRC, which was observed in clinical practice is associated with the severity of health behavior.

Immunohistochemical Predictors of Bone Metastases in Breast Cancer Patients.

Bones are the most common metastatic site of relapse in breast cancer patients and the prediction of bone metastases (BM) risk might prompt developing preventive and therapeutic strategies. The aim of the study was to correlate immunohistochemical (IHC) expression of selected proteins in primary breast cancer with the occurrence of BM. We analyzed expression of proteins potentially associated with BM in primary tumors of 184 patients with metastatic breast cancer (113 with- and 71 without BM). Expression of estrogen receptor (ER) in primary tumor was more common in patients with- compared to those without BM (74 vs. 45 % respectively, p = 0.0001), whereas in this subset less common was expression of parathyroid hormone related protein receptor type 1 (16 vs. 34 %, respectively, p = 0.007) and cytoplasmic expression of osteopontin (OPNcyt; 1.9 vs. 14 %, respectively, p = 0.002). The relationship between expression of ER and OPNcyt and the occurrence of BM was confirmed in the multivariate analysis. The ER-positive/OPNcyt negative phenotype was significantly more common in patients with- compared to those without BM (75 and 25 %, p < 0.0001, respectively; HR 1.79, p = 0.013). Luminal A (43 vs. 23 % respectively, p = 0.009) and luminal B/HER2-positive (16 vs. 4.9 % respectively, p = 0.032) subtypes were more common in patients with- compared to those without BM, whereas triple negative breast cancer subtype was less common (16 vs. 38 %, p = 0.002).

Body mass index as a predictor of colorectal cancer.

INTRODUCTION: Colorectal cancer is the second most common cancer in the world. Each year in Poland, 16 000 people are diagnosed with colorectal cancer and 9 000 patients die of it. Factors that may increase a chance of developing colorectal cancer include: male sex, advanced age, smoking, and positive family history of this condition. Recently, scientists have discovered that obesity also belongs to the group of risk factors. The present research aims at establishing whether there exists any relationship between BMI and colorectal cancer in Poland. METHODS: This research is based on the analysis of the results of a clinical study conducted in the period from May 2011 to December 2014 in another group of 319 patients undergoing colonoscopy in the district hospital in Wejherowo. Colonoscopy results were compared between 136 patients with colorectal cancer and/or dysplastic polyps and 167 healthy patients. RESULTS: The study revealed that the number of males, elderly people, and smokers was much bigger among patients with colon abnormalities than among healthy people. The multiple factor analysis demonstrates that the body mass index (BMI) was significantly higher among men and women diagnosed with colorectal cancer as compared to healthy patients. Both overweight (BMI reaching from 25.0 to 29.9 kg/m2) and obesity (BMI≥30 kg/m2) were independent risk factors associated with colorectal cancer. CONCLUSIONS: An increased BMI should also be considered as an independent risk factor for colorectal cancer in the Polish population. This may indicate a need for conducting and increasing the frequency of colonoscopic examinations among patients with high BMI in Poland.

Evaluation of the Impact of Different Types of Health Education on the Adoption and Preservation of Prohealth Attitudes in Preventing Cancer in Juveniles Younger than 18 Years.

Reduction in the incidence of cancer can be achieved through appropriate health behaviors. We hypothesized that education would improve knowledge of cancer prevention, and this, in turn, will affect and individual's readiness to modify lifestyle. The aim of this study was to assess the impact of cancer prevention education on adopting and preserving prohealth attitudes among high school students in Poland. Research participants were 307 high school students varying by gender, place of residence, parents' education, and type of school education. Participants were divided into five groups, of which four were educated using different methods according to classification methods based on the concept of multilateral learning. The fifth (control) group was not educated. The effects of education were assessed 1 month and 1 year after education. General knowledge about cancer and healthy lifestyle level before education was low. After education, both increased compared with the control group. There was a clear relationship between level of knowledge and readiness to adopt and healthy attitudes and behavior. The most effective method of education was a discussion and a lecture by means of teaching complex. Education significantly improved generally low knowledge about cancer and healthy lifestyle in high school students. This indicates the urgent need to implement such educational programs.

Assessment of quality of life in advanced non-small-cell lung cancer: an overview of recent randomized trials.

BACKGROUND: Health-related quality of life (HRQOL) parameters are often used as secondary endpoints in advanced non-small-cell lung cancer (NSCLC). We assessed the frequency and correlates of both usage and gain in HRQOL endpoints in NSCLC phase III trials. METHODS: We searched PubMed for phase III trials on systemic anticancer therapies for NSCLC published between 1/98 and 12/09 in 13 leading journals. RESULTS: The search yielded 122 trials that enrolled a total of 56,031 patients in 273 trial arms. HRQOL was reportedly used as an endpoint in 72 trials (59%). HRQOL parameters were used as primary or co-primary endpoints in nine trials, whereas overall survival (OS) was the primary endpoint or one of the co-primary endpoints in 90 trials. There was no temporal trend for usage of HRQOL parameters as endpoints. Formal statistical comparisons involving HRQOL were reported in 68/72 cases, and a significant difference was found in 37/68 trials (54.4%), 24 of which favored the experimental arm. In many cases, such differences were restricted to specific symptoms or even favored more than one regimen according to symptoms analyzed. We found no significant association between gain in HRQOL and gain in OS or any other trial feature. CONCLUSIONS: HRQOL has been assessed formally in nearly 60% of contemporary phase III trials in advanced NSCLC, and a significant gain in HRQOL has been found in almost one-half of cases. It is questionable, however, whether HRQOL results may help select between treatments with no differential impact on OS.

Assessment of quality of life in advanced breast cancer. An overview of randomized phase III trials.

BACKGROUND: Health-related quality of life (HRQOL) parameters are often used as end points in phase III trials in advanced breast cancer. The frequency and correlates of significant gains in HRQOL have not been assessed. METHODS: To evaluate the contemporary role for HRQOL assessment in advanced breast cancer, we searched PubMed for the main and companion papers reporting the results of phase III trials on systemic antineoplastic therapies published between 1/98 and 7/09 in 11 leading journals. RESULTS: The search yielded 87 trials that enrolled a total of 33,669 patients. HRQOL was mentioned/reported in the main paper in 34 trials, reported in a companion paper in one (a total of 35/87=40%), and mentioned in the abstract of the main paper in 19/34 cases (56%). There was no temporal trend for reporting on HRQOL in the two 6-year periods. Although formal statistical comparisons were reported in 31/35 cases (89%), a significant difference was found in only 4/31 (13%) trials, always favoring the experimental arm. Given the small number of studies with a significant HRQOL finding, we could not assess correlates of gain in HRQOL. CONCLUSIONS: HRQOL is one of the key indicators of treatment benefit in advanced breast cancer, but contemporary systemic therapies in this setting do not appear to affect HRQOL differentially.

Combining systemic therapies with radiation in breast cancer.

Over the last years, significant survival benefits for breast cancer were derived from the use of postoperative systemic therapies and radiotherapy. Although these two modalities have been extensively used, the optimal strategies of their combining remain debatable. There have been few randomized studies addressing this issue and their results are generally inconclusive. This article reviews combining systemic therapies (chemotherapy, hormonotherapy and trastuzumab) with radiation in breast cancer patients. In clinical practice, chemotherapy and radiotherapy are most commonly used sequentially but this strategy is not based on level 1 evidence. Increased cardiotoxicity and skin reactions preclude the concomitant radiotherapy and anthracycline-based chemotherapy. Further investigations are warranted to determine the safety of taxane-based schedules used concomitantly with radiotherapy, particularly with regard to pneumotoxicity. Concurrent chemo-radiotherapy with the use of selected schemes may be considered in patients with locally advanced cancer but this strategy still needs to be verified in large randomized studies. The optimal combination of tamoxifen and aromatase inhibitors with radiotherapy has also not been determined in randomized trials and the results of retrospective studies are inconsistent. Finally, the data on combining targeted therapies with radiation are still scarce and do not allow for meaningful conclusions.