Radiation recall dermatitis: A review of the literature.

PURPOSE/OBJECTIVES: Radiation recall dermatitis (RRD) is a skin reaction limited to an area of prior radiation triggered by the subsequent introduction of systemic therapy. To characterize RRD, we conducted a literature search, summarized RRD features, and compared the most common drug classes implicated in this phenomenon. MATERIALS/METHODS: PubMed, Embase, Scopus, Web of Science, and Cochrane DBSR databases were queried through July 1, 2019 using key words: radiation recall, RRD, and radiodermatitis (limited to humans and English language). Studies included case reports in which patients treated with radiotherapy were initiated on a new line of systemic therapy and subsequently developed a skin reaction in the irradiated area. RRD cases were organized by whether RRD occurred after a single drug or multiple drug administration. RESULTS: One-hundred fifteen studies representing 129 RRD cases (96 single-drug RRD, 33 multi-drug) were included. Sixty-three drugs were associated with RRD. Docetaxel (22) and gemcitabine (18) were the two drugs most commonly associated with RRD. Breast cancer (69 cases) was the most commonly associated tumor type. For single-drug RRD, the median radiotherapy dose was 45.0 Gy (range, 30.0-63.2 Gy). The median time from radiotherapy to drug exposure, time from drug exposure to RRD and time to significant improvement was 8 weeks (range, 2-132 weeks), 5 days (range, 2-56 days), and 14 days (range, 7-49 days), respectively. Variables significantly associated with grade ≥2 toxicity were docetaxel (P = 0.04) and non-antifolate antimetabolite (P = 0.05). The only variable significantly associated with grade ≥3 toxicity was capecitabine (P = 0.04). CONCLUSIONS: RRD is a complex toxicity that can occur after a wide range of radiotherapy doses and many different systemic agents. Most commonly, it presents in patients diagnosed with breast cancer and after administration of a taxane or antimetabolite medication. RRD treatment generally consists of corticosteroids with consideration of antibiotics if superinfection is suspected. Drug re-challenge may be considered after RRD if the initial reaction was of mild intensity.

Modeling of Acute Rectal Toxicity to Compare Two Patient Positioning Methods for Prostate Cancer Radiotherapy: Can Toxicity Modeling be Used for Quality Assurance?

PURPOSE: Intensity Modulated Radiation Therapy (IMRT) allows for significant dose reductions to organs at risk in prostate cancer patients. However, the accurate delivery of IMRT plans can be compromised by patient positioning errors. The purpose of this study was to determine if the modeling of grade ≥ 2 acute rectal toxicity could be used to monitor the quality of IMRT protocols. MATERIALS AND METHODS: 79 patients treated with Image and Fiducial Markers Guided IMRT (FMIGRT) and 302 patients treated with trans-abdominal ultrasound guided IMRT (USGRT) was selected for this study. Treatment plans were available for the FMIGRT group, and hand recorded dosimetric indices were available for both groups. We modeled toxicity in the FMIGRT group using the Lyman Kutcher Burman (LKB) and Univariate Logistic Regression (ULR) models, and we modeled toxicity in USGRT group using the ULR model. We performed Receiver Operating Characteristics (ROC) analysis on all of the models and compared the Area under the ROC curve (AUC) for the FMIGRT and the USGRT groups. RESULTS: The observed Incidence of grade ≥ 2 rectal toxicity was 20% in FMIGRT patients and 54% in USGRT patients. LKB model parameters in the FMIGRT group were TD50=56.8 Gy, slope m=0.093, and exponent n=0.131. The most predictive indices in the ULR model for the FMIGRT group were D25% and V50 Gy. AUC for both models in the FMIGRT group was similar (AUC=0.67). The FMIGRT URL model predicted less than a 37% incidence of grade ≥ 2 acute rectal toxicity in the USGRT group. A fit of the ULR model to USGRT data did not yield a predictive model (AUC=0.5). CONCLUSION: Modeling of acute rectal toxicity provided a quantitative measure of the correlation between planning dosimetry and this clinical endpoint. Our study suggests that an unusually weak correlation may indicate a persistent patient positioning error.

Predictors of survival in patients with brain metastases from gastric cancer.

This study aims to identify predictors of survival and contribute to treatment personalization in patients with brain metastases from gastric cancer. Twelve patients received whole-brain radiotherapy (WBRT), four stereotactic radiosurgery and six neurosurgery plus WBRT. Treatment regimen, age, gender, Eastern Cooperative Oncology Group (ECOG) performance score, tumor site, number of brain metastases, extra-cranial metastases and interval between cancer diagnosis and brain metastases were evaluated for survival. On univariate analyses, more intensive treatment (p=0.003), ECOG-score 0-1 (p<0.001), cardiac location (p=0.025) and single brain metastasis (p=0.023) were associated with better survival. On multivariate analysis, ECOG-score maintained significance (p<0.001). Patients with all three positive factors on univariate analysis had a 12-month survival rate of 100%, patients with three negative factors a 3-month survival rate of 0%. Predictors of survival were identified that can guide physicians selecting personalized treatment approaches for patients with brain metastases from gastric cancer.

Pathways to improving combined modality therapy for stage III nonsmall-cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer deaths, having caused an estimated 1.6 million deaths worldwide in 2012 [Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-E386]. MATERIALS AND METHODS: Although the majority of patients are not cured with currently available therapies, there have been significant improvements in stage-specific outcomes over time [Videtic G, Vokes E, Turrisi A et al. The survival of patients treated for stage III non-small cell lung cancer in North America has increased during the past 25 years. In The 39th Annual Meeting of the American Society of Clinical Oncology, ASCO 2003, Chicago, IL. Abstract 2557. p. 291]. This review focuses on past progress and ongoing research in the treatment of locally advanced, inoperable nonsmall-cell lung cancer (NSCLC). RESULTS: In the past, randomized trials revealed advantages to the use of thoracic radiotherapy (TRT) and then, the addition of induction chemotherapy. This was followed by studies that determined concurrent chemoradiotherapy to be superior to sequential therapy. A recent large phase III trial found that the administration of 74 Gy of conventionally fractionated photon-based TRT provided poorer survival than did the standard 60 Gy. However, further research on other methods of applying radiotherapy (hypofractionation, adaptive TRT, proton therapy, and stereotactic TRT boosting) is proceeding and may improve outcomes. The molecular characterization of tumors has provided more effective and less toxic targeted treatments in the stage IV setting and these agents are currently under investigation for earlier stage disease. Similarly, immune-enhancing therapies have shown promise in stage IV disease and are also being tested in the locally advanced setting. CONCLUSION: For locally advanced, inoperable NSCLC, standard therapy has evolved from TRT alone to combined modality therapy. We summarize the recent clinical trial experience and outline promising areas of investigation in an era of greater molecular and immunologic understanding of cancer care.

A new prognostic factor for the survival of patients with renal cell carcinoma developing metastatic spinal cord compression.

BACKGROUND AND PURPOSE: This study aimed to identify a potential association of the number of involved extraspinal organs with the survival of patients with metastatic spinal cord compression (MSCC) from renal cell carcinoma. PATIENTS AND METHODS: Data of 69 patients irradiated for MSCC from renal cell carcinoma were retrospectively evaluated for survival. The prognostic value of the number of involved extraspinal organs and eight additional factors were investigated. These additional factors included age, gender, performance status, number of involved vertebrae, interval from cancer diagnosis to radiotherapy (RT) of MSCC, ambulatory status prior to RT, time developing motor deficits, and the fractionation regimen (30 Gy in 10 fractions vs. higher doses). RESULTS: The 6-month survival rates for involvement of 0, 1, and ≥ 2 extraspinal organs were 93, 57, and 21%, respectively (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs maintained significance (risk ratio 2.65; 95% confidence interval 1.64-4.52; p < 0.001). The interval from cancer diagnosis to RT of MSCC (p = 0.013) and ambulatory status prior to RT (p = 0.002) were also independent predictors of survival. CONCLUSION: The number of involved extraspinal organs is a new prognostic factor of survival in patients with MSCC from renal cell carcinoma and should be considered in future clinical trials.

Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer.

BACKGROUND AND PURPOSE: This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. MATERIALS AND METHODS: Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. RESULTS: The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤ 50 and ≥ 4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50 patients had KPS ≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. CONCLUSION: The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases.

Brain metastasis from non-small cell lung cancer (NSCLC): prognostic importance of the number of involved extracranial organs.

BACKGROUND AND PURPOSE: This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 × 4 Gy or 10 × 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung + bone vs. lung+lymph nodes vs. other combinations) extracranial organs. RESULTS: The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥ 4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥ 70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. CONCLUSION: The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement.

Breast cancer patients with metastatic spinal cord compression. Number of extraspinal organs involved by metastases influences survival.

BACKGROUND AND PURPOSE: The goal of the present work was to investigate the predictive value of the number of extraspinal organs involved by metastases for the survival of patients with metastatic spinal cord compression (MSCC) from breast cancer. PATIENTS AND METHODS: Data of 145 breast cancer patients who received 10 fractions of 3 Gy of radiotherapy (RT) alone for MSCC were retrospectively analyzed. Seven potential prognostic factors were investigated including age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, interval from breast cancer diagnosis to RT of MSCC, ambulatory status prior to RT, time to developing motor deficits, and the number of involved extraspinal organs. RESULTS: The 1-year survival rates for involvement of 0, 1, 2, and ≥ 3 extraspinal organs were 86, 73, 36, and 16 % (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs remained significant (risk ratio 2.19; 95 % confidence interval 1.61-3.00; p < 0.001). ECOG performance score (p < 0.001), ambulatory status prior to RT (p = 0.003), and the time to developing motor deficits (p < 0.001) were also significantly associated with survival in the multivariate analysis. CONCLUSION: The number of extraspinal organs involved by metastases is an independent prognostic factor of survival in patients with MSCC from breast cancer.

Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. PATIENTS AND METHODS: The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. RESULTS: On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95%-confidence interval (CI): 2.88-19.05; p<0.001], lower T-category (RR: 2.42; 95%-CI: 1.47-4.33; p<0.001), lower N-category (RR: 12.36; 95%-CI: 3.48-78.91; p<0.001), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 4.18; 95%-CI: 1.73-10.53; p=0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95%-CI: 0.97-2.82; p=0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p<0.001), lower T-category (RR: 2.17; 95%-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95%-CI: 1.60-10.85; p=0.002), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 3.20; 95%-CI: 1.46-7.30; p=0.004). HPV-positivity showed a trend (RR: 2.36; 95%-CI: n.a.; p=0.054). CONCLUSIONS: Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials.

A survival score for patients with brain metastases from less radiosensitive tumors treated with whole-brain radiotherapy alone.

BACKGROUND AND PURPOSE: This study aimed to develop and validate a scoring system to predict the survival of patients receiving whole-brain radiotherapy (WBRT) alone for brain metastases from less radiosensitive tumors. PATIENTS AND METHODS: The study included data from 176 patients with brain metastasis from renal cell carcinoma, malignant melanoma or colorectal cancer. Patients were divided into a test group (N=88) and a validation group (N=88). In the multivariate analysis of the test group, age, Karnofsky Performance Status and extracranial metastasis were significantly associated with survival. These three factors were included in the scoring system. The score for each factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the three scores. According to the total scores-which ranged from 5 to 14 points-three prognostic groups were created. RESULTS: The 6-month survival rates in the test group were 11% for 5-8 points (N=47, group A), 38% for 9-11 points (N=29, group B) and 83% for 12-14 points (N=12, group C). In the validation group the 6-month survival rates were 12, 31 and 75%, respectively. Comparisons between the prognostic groups A, B and C of the test group with those of the validation group did not reveal any significant differences. CONCLUSION: The new scoring system based on three independent prognostic factors can help to estimate the survival of patients with brain metastases from a less radiosensitive tumor. The score appears to be valid and reproducible.

Brain metastasis. Prognostic value of the number of involved extracranial organs.

BACKGROUND AND PURPOSE: This study was performed to evaluate the prognostic role for survival of the number and the type of involved extracranial organs in patients with brain metastasis. MATERIAL AND METHODS: The data of 1146 patients who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been retrospectively analyzed. In addition to the number of involved extra cranial organs, seven potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type, number of brain metastases, and the interval from cancer diagnosis to WBRT. Additionally, subgroup analyses were performed for patients with involvement of one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations) extracranial organs. RESULTS: The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 51, 30, 16, 13, and 10%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs maintained significance (risk ratio 1.26; 95% confidence interval 1.18-1.34; p<0.001). According to the multivariate analysis, age (p<0.001), gender (p=0.002), and KPS (p<0.001) were also independent prognostic factors for survival. In the subgroup analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the extracranial organ involved. CONCLUSION: The number of involved extracranial organs proved to be an independent prognostic factor in patients with brain metastasis, regardless of the organs involved. The number of involved extracranial organs should be considered in future trials designed for patients with brain metastasis.

Androgen receptor expression: prognostic value in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of androgen receptor (AR) expression of tumor cells in patients treated with surgery and subsequent radio(chemo)therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: The impact of AR and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively studied in 163 patients with nonmetastatic stage III/IV SCCHN. Additional factors included age, gender, ECOG performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, HPV status, extent of resection, and concurrent chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with pre-RT hemoglobin levels≥12 g/dl (risk ratio [RR] 2.22; 95% confidence interval [CI] 1.19­4.13; p=0.013), tumor site (RR 1.39; 95% CI 1.14­1.70; p=0.001), lower T category (RR 1.67; 95% CI 1.18­2.44; p=0.003), and lower N category (RR 4.18; 95% CI 1.90­10.55; p<0.001). Improved MFS was associated with AR expression (RR 2.21; 95% CI 1.01­5.41; p=0.048), better ECOG performance status (RR 3.19; 95% CI 1.50­7.14; p=0.003), lower T category (RR 2.24; 95% CI 1.47­3.65; p<0.001), and lower N category (RR 5.33; 95% CI 2.07­16.63; p<0.001). OS was positively associated with AR expression (RR 1.99; 95% CI 1.06­4.00; p=0.032), better ECOG performance status (RR 2.20; 95% CI 1.20­4.09; p=0.010), pre-RT hemoglobin levels≥12 g/dl (RR 2.13; 95% CI 1.19­3.82; p=0.012), lower T category (RR 1.81; 95% CI 1.30­2.62; p<0.001), and lower N category (RR 3.41; 95% CI: 1.65­7.80; p<0.001). CONCLUSION: Tumor cell expression of AR was an independent prognostic factor for MFS and OS and should be considered in future prospective trials.

Impact of the HPV-positivity definition on the prognostic value of HPV status in patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study re-evaluated the prognostic value of HPV status for loco-regional control (LRC), metastases-free survival (MFS), and survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). A modified definition of HPV positivity was used in the current study compared to the authors' previous study. PATIENTS AND METHODS: In the previous study of the same 170 patients, a tumor was defined as HPV-positive if it showed a positive in situ hybridization result in ≥10% of tumor cells and/or positive p16 immunostaining. In the current analysis, tumors were considered HPV-positive only if they showed positive results for both in situ hybridization and p16 immunostaining. In addition to HPV status, the same 11 potential prognostic factors were investigated for treatment outcomes as in the preceding study. RESULTS: In the multivariate analysis of the current study, HPV positivity was significantly associated with improved LRC [risk ratio (RR) 9.78; p<0.001], MFS (RR 7.17; p=0.008), and OS (RR 6.61; p<0.001). In the previous study, HPV positivity was associated with LRC (RR 2.34; p=0.014) and OS (RR 2.19; p=0.019), but not with MFS (RR 2.04; p=0.11). CONCLUSIONS: Applying the new definition of HPV positivity, the impact of HPV status on the prognosis of patients irradiated for locally advanced SCCHN was more prominent than in our previous study and associated with all three investigated endpoints.

A new survival score for patients with brain metastases from non-small cell lung cancer.

BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) is the most common primary tumor in patients developing brain metastasis. This study was performed to develop and validate a survival score particularly for this group of patients. PATIENTS AND METHODS: In this study, the data of 514 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastasis from NSCLC were retrospectively analyzed. The patients were divided into a test group (n = 257) and a validation group (n = 257). In the multivariate analysis of the test group, gender, performance status, and extracranial metastases were independent predictors of survival and, therefore, included in the scoring system. The score for each of the three factors was obtained from the 6-month survival rate (in %) divided by 10. The total scores that represented the sum of the three scores were 5, 8, 9, 11, 12, or 15 points. Three prognostic groups were formed according to the total scores. RESULTS: The 6-month survival rates in the test group were 9 % for 5-9 points (group A), 54 % for 11-12 points (group B), and 79 % for 15 points (group C). In the validation group the 6-month survival rates were 14, 56, and 78 %, respectively. The comparisons between the prognostic groups A, B, and C of the test and the validation group did not reveal any significant differences. CONCLUSION: This new score appears valid and reproducible. It can help predict the survival of patients with brain metastasis from NSCLC.

A simple survival score for patients with brain metastases from breast cancer.

BACKGROUND AND PURPOSE: Personalized cancer treatment considers the patient's survival prognosis. Therefore, it is important to be able to estimate the patient's survival time, particularly in a palliative situation such as brain metastasis. This study aimed to create and validate a survival score for patients with brain metastasis from breast cancer, which is the second most common primary tumor in these patients. PATIENTS AND METHODS: Data of 230 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastasis from breast cancer were retrospectively analyzed. Patients were assigned to a test (n = 115) or a validation group (n = 115). According to the results of the multivariate analysis of the test group, Karnofsky Performance Score and extracranial metastases were included in the scoring system. The score for each factor was obtained from the 6-month survival rate (in %) divided by 10. Total scores represented the sum of these scores and were 4, 7, 9, or 12 points. Three prognostic groups were formed. RESULTS: The 6-month survival rates in the test group were 10 % for 4-7 points, 55 % for 9 points, and 78 % for 15 points (p < 0.001). In the validation group the corresponding 6-month survival rates were 11, 54, and 75 %, respectively (p < 0.001). The comparisons between the prognostic groups of the test and the validation group did not show significant differences. CONCLUSION: This simple survival score appears valid and reproducible. It can be used to estimate the survival time of patients with brain metastasis from breast cancer receiving WBRT alone.

Prognostic impact of VEGF and FLT-1 receptor expression in patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of tumor cell expression of vascular endothelial growth factor (VEGF) and its receptor fms-related tyrosine kinase 1 (FLT-1) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who had been treated with adjuvant radiotherapy or radiochemotherapy. MATERIAL AND METHODS: The impact of tumor cell VEGF and FLT-1 expression plus 11 additional factors on loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) was retrospectively evaluated in 157 patients. The additional factors were age, gender, performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papillomavirus (HPV) status, extent of resection and chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with an absence of VEGF expression (risk ratio, RR: 5.02; p = 0.009), lower T-category (RR: 2.00; p < 0.001), lower N-category (RR: 3.75; p < 0.001) and pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.20; p = 0.029). Improved MFS was significantly associated with an absence of VEGF expression (RR: 7.46; p = 0.002), lower T-category (RR: 1.97; p = 0.002), lower N-category (RR: 3.29; p = 0.005) and a favorable tumor location (RR: 1.34; p = 0.033); HPV positivity showed a trend towards improved MFS (RR: 1.43; p = 0.09). Improved OS was significantly associated with an absence of VEFG expression (RR: 3.22; p = 0.041), pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.47; p = 0.009), lower T-category (RR: 1.92; p < 0.001) and lower N-category (RR: 3.39; p < 0.001). FLT-1 expression was significantly associated with LRC and OS in the univariate but not in the multivariate analysis. CONCLUSION: VEGF expression proved to be an independent negative predictor for LRC, MFS and OS in patients treated for locally advanced SCCHN with adjuvant radiotherapy or radiochemotherapy. FLT-1 expression was not significant in multivariate analyses.

Prognosis of patients with locally advanced squamous cell carcinoma of the head and neck. Impact of tumor cell expression of EPO and EPO-R.

BACKGROUND AND PURPOSE: This study investigated the prognostic role of tumor cell expression of erythropoietin (EPO) and its receptor (EPO-R) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with surgery plus radiotherapy. PATIENTS AND METHODS: The impact of EPO, EPO-R, and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 144 patients. Additional factors were age, gender, performance status, preradiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, human papillomavirus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. RESULTS: On multivariate analysis, improved LRC was significantly associated with no EPO expression (risk ratio [RR] 3.72; 95 % confidence interval [CI] 1.35-15.42; p = 0.008), lower T category (RR 1.60; 95 %CI 1.14-2.32; p = 0.005), and oropharynx or larynx cancer (RR 1.23; 95 %CI 1.02-1.49; p = 0.033). Improved MFS was significantly associated with no EPO expression (RR 5.45; 95 %CI 1.13-97.81; p = 0.031), lower T category (RR 1.66; 95 %CI 1.11-2.65; p = 0.013), lower N category (RR 2.44; 95 %CI 1.04-6.66; p = 0.039), HPV positivity (RR 3.14; 95 %CI not available; p = 0.034), and oropharynx or larynx cancer (RR 1.28; 95 %CI 1.01-1.61; p = 0.041). Improved OS was significantly associated with no EPO expression (RR 4.77; 95 %CI 1.63-20.68; p = 0.003), no EPO-R expression (RR 2.36; 95 %CI 1.22-4.92; p = 0.010), lower T category (RR 1.44; 95 %CI 1.04-2.04; p = 0.027), oropharynx or larynx cancer (RR 1.30; 95 %CI 1.08-1.57; p = 0.007), and pre-RT hemoglobin ≥ 12 g/dl (RR 1.94; 95 %CI 1.03-3.65; p = 0.042). CONCLUSION: EPO expression of tumor cells was an independent prognostic factor for LRC, MFS, and OS. EPO-R expression was an independent prognostic factor for OS.

A validated scoring system to identify long-term survivors after radiotherapy for metastatic spinal cord compression.

PURPOSE: This study aimed to develop and validate a scoring system to identify long-term survivors after conventional radiotherapy (RT) for metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Data from 1,125 patients who had received long-course RT for MSCC were included in this study. Of these patients, 344 survived for over 12 months and 781 died within a year following RT. Based on differences between the distributions of patient characteristics in the two groups, a scoring system was developed. Scores ranged from 0 to 18 points and 15 points was selected as the cutoff for identifying long-term survivors. Data from the 1,125 long-course RT patients (test group) were compared to data from 773 patients receiving short-course RT (validation group). RESULTS: A score of ≥ 15 points was associated with a 94 % proportion of long-term survivors. The 15-point cutoff resulted in a specificity of 98 % and a positive predictive value of 94 % for identification of long-term surviving patients. The proportions of long-term survivors for each scoring point in the validation group were very similar to those in the test group. CONCLUSION: This new scoring system enabled identification of long-term survivors after RT for MSCC with very high specificity and positive predictive value. The score proved to be valid and reproducible.

Validation of a survival score for patients treated with whole-brain radiotherapy for brain metastases.

BACKGROUND: This study was performed to validate a scoring system published in 2008 to predict the survival of patients receiving whole-brain radiotherapy (WBRT) alone for brain metastases. METHODS: The scoring system included four independent prognostic factors: age, performance status, extracranial metastases, and interval between first diagnosis of cancer and WBRT. The score for each prognostic factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the scores for each prognostic factor. Total scores ranged from 9-18 points, and patients were divided into four groups. In the present study, 350 new patients were evaluated in order to validate the previously developed score. RESULTS: In the present validation study, the 6-month survival rates were 8 % for patients with a score of 9-10 points (group A), 24 % for those with a score of 11-13 points (group B), 51 % for those with a score of 14-16 points (group C), and 82 % for those with scores of 17-18 points (group D), respectively (p < 0.001). In our previous study published in 2008, the 6-month survival rates were 6 %, 15 %, 43 %, and 76 %, respectively (p < 0.001). The comparisons between each of the four prognostic groups of both series did not reveal a significant difference. CONCLUSION: In this study, the 6-month survival rates of the four prognostic groups were not significantly different from those of the preceding study. This demonstrates the validity and reproducibility of this score. The score can help select the appropriate treatment for the individual patient and help design prospective trials.

A validated survival score for breast cancer patients with metastatic spinal cord compression.

BACKGROUND: To create a validated scoring system predicting survival of breast cancer patients with metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Of 510 patients, one half were assigned to either the test or the validation group. In the test group, eight pretreatment factors (age, performance status, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time of developing motor deficits) plus the radiation regimen were retrospectively investigated. Factors significantly associated with survival in the multivariate analysis were included in the scoring system. The score for each factor was determined by dividing the 6-month survival rate (%) by ten. The total score was the sum of the scores for each factor. RESULTS: In the multivariate analysis of the test group, performance status, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and time of developing motor deficits were significant for survival and included in the score. Total scores ranged from 30 to 50 points. In the test group, the 6-month survival rates were 12% for 30-35 points, 41% for 36-40 points, 74% for 41-45 points, and 98% for 46-50 points (p < 0.0001). In the validation group, the 6-month survival rates were 14%, 46%, 77%, and 99%, respectively (p < 0.0001). CONCLUSION: The survival rates of the validation group were similar to the test group. Therefore, this score was reproducible and can help when selecting the appropriate radiotherapy regimen for each patient taking into account her survival prognosis.