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.

Trends of maxillofacial trauma: An update from the prospective register of a multicenter study in emergency services of Chile.

BACKGROUND: Determine the behavior of the maxillofacial trauma of adults treated in 3 tertiary care centers in the central zone of Chile. MATERIAL AND METHODS: descriptive, cross-sectional, multicenter study, based on the prospective records of maxillofacial trauma cases attended between May 2016 and April 2017 by dental and maxillofacial clinical teams of Adult Emergency Units of hospitals Dr. Sótero del Río (metropolitan region), Carlos Van Buren and Dr. Gustavo Fricke (region V). Age, sex, date of occurrence, type of trauma according to ICD-10, etiology, legal medical prognosis and associated injuries were recorded, stratifying by sex and age. Chi square and unpaired Wilcoxon tests were used to compare by groups. RESULTS: 2.485 cases and 3.285 injuries were investigated. The male: female ratio was 1.7: 1 with age under 30 predominant, followed by older adults. Variability was observed in the yearly, weekly and daily presentation. The highest frequencies were in January and September, weekends and at night. The main etiologies were violence (42.3%), falls (13.1%) and road traffic crashes (12.9%) with differences by age and sex (p <0.05). 31,9% of the injuries occurred in hard tissue, being fractures in nasal bones predominant (S02.2). CONCLUSIONS: the profile of the maxillofacial trauma in Chile seems to be mixed by age, affecting young people and the elderly. The male sex predominates; the main cause, which varies by age group, is violence. Their surveillance is possible from hospital emergency records.

Does hut climate matter for piglet survival in organic production?

Piglet mortality in outdoor production systems varies across the year, and a reason for this variation could be fluctuations in hut climate, as ambient temperature might influence piglet survival, both directly and indirectly. Therefore, the aim of the current study was to investigate the impact of farrowing hut climate and year variation on stillbirth and liveborn mortality. A large-scale observational study was conducted at five commercial organic pig-producing herds in Denmark from June 2015 to August 2016. Both year variation (F 3,635=4.40, P=0.004) and farrowing hut temperature (F 2,511=6.46, P=0.002) affected the rate of stillbirths. The risk of stillborn piglets was lowest in winter and during this season larger changes in hut temperature between day 1 prepartum and the day of farrowing increased the risk of stillbirths (F 1,99=6.39, P=0.013). In addition, during the warm part of the year stillbirth rate increased at temperatures ⩾27°C. Year variation also affected liveborn mortality (F 3,561=3.86, P=0.009) with a lower rate of liveborn deaths in spring. However, the hut climate did not influence liveborn deaths. Consequently, other factors than hut climate may explain the influence of year variation on liveborn mortality. These could be light differences causing seasonality in reproduction and lactation.

Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention.

PURPOSE: To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. METHODS: Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T­category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (

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.

The effect of varying duration of water restriction on drinking behaviour, welfare and production of lactating sows.

Access to drinking water is essential for animal welfare, but it is unclear if temporary water restriction during the night represents a welfare problem. The aim of the present study was to investigate the effect of various durations of nightly restriction of water on thirst in loose housed lactating sows from day 10 to 28 of lactation. A total of 48 sows were deprived of water for either 0 h (n=12; control), 3 h (n=12; 0500 to 0800 h), 6 h (n=12; 0200 to 0800 h) or 12 h (n=12; 2000 to 0800 h). Control sows consumed 22% of their water intake during the night (2000 to 0800 h), whereas water consumption during this time was reduced to 13%, 7% and 0% in sows restricted for 3, 6 and 12 h. With increased duration of nightly water restriction a reduced latency to drink (26.8, 18.0, 5.3 and 6.7 min for 0, 3, 6 and 12 h sows; P<0.001) and an increased water intake during the 1st hour after water became accessible (2.1, 3.4, 4.7 and 5.6 l for 0, 3, 6 and 12 h sows; P<0.001) was seen. During the last 30 min before water became accessible more sows deprived of water investigated (0%, 50%, 75%,and 50% of 0, 3, 6 and 12 h sows; P<0.01) or forcefully manipulated (0%, 17%, 50% and 33% of 0, 3, 6 and 12 h sows; P<0.05) the water trough, suggesting frustration and a negative experience of thirst. When all signs of imminent water access were provided, but access was delayed by 25 min, a tendency for more of the sows deprived of water for 6 and 12 h to interact forcefully with the water trough was seen (22%, 18%, 42% and 67% of 0, 3, 6 and 12 h sows; P=0.09). Duration of water restriction did not affect water consumption on a 24-h basis, nursing behaviour or performance. In conclusion, behavioural indicators of thirst increased with increasing duration of nightly water restriction in lactating sows.

The influence of the thermal environment and other early life events on growth rate of piglets during lactation.

The effects of early life events on average daily weight gain from birth to day 21 (ADG) of suckling pigs kept at different room temperatures (15°C, 20°C and 25°C) from birth to weaning were investigated. Data were collected from litters born by 61 sows in a loose housing system. The ADG for piglets with low birth weight (estimated for birth weights below the 10% percentile) was estimated to be 20 to 30 g higher per day at room temperature 20°C to 25°C compared with 15°C. In contrast, the ADG during the lactation period decreased for larger piglets (estimated for birth weights above the 10% percentile) by 28 g/day at room temperature 25°C compared with 15°C. Thus, high ambient temperatures (20°C to 25°C) are favourable for the growth in smaller piglets during lactation. Neither latency to first suckle nor birth-induced hypoxia, measured as concentration of umbilical cord lactate, affected the growth rate of the piglets. Lowest rectal temperature during the first 24 h after birth had a long-term negative effect on ADG (P<0.05), so that piglets with a lowest rectal temperature of 32.8°C (10% percentile) had an ADG which was on average 19 g lower per day than piglets with a rectal temperature of 37.3°C (90% percentile). Our results showed that hypothermia at birth, low birth weight and high number of suckling piglets lead to reduced ADG during the suckling period. The results suggest that keeping the room temperature at 20°C during lactation to some extent could compensate for the otherwise negative effects of low birth weight on ADG in piglets without decreasing the ADG of high birth weight piglets. However, to avoid hypothermia in the smallest piglets it may be beneficial to increase the room temperature above 20°C during the farrowing period of loose housed sows.

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.

Wake-up Strokes Are Similar to Known-Onset Morning Strokes in Severity and Outcome.

BACKGROUND: Stroke symptoms noticed upon waking, wake-up stroke, account for up to a quarter of all acute ischemic strokes. Patients with wake-up stroke, however, are often excluded from thrombolytic therapy. METHODS: Using our prospectively collected stroke registry, wake-up stroke and known-onset morning strokes were identified. Wakeup stroke was defined as a patient who was asleep >3 hours and first noted stroke symptoms upon awakening between 0100 and 1100. Known-onset morning stroke was defined as a patient who had symptom onset while awake during the same time interval. We compared wake-up stoke to known-onset morning stroke with respect to patient demographics, stroke severity, etiology and outcomes. RESULTS: One-quarter of patients with acute ischemic strokes (391/1415) had documented time between 0100 and 1100 of symptom onset: 141 (36%) wake-up strokes and 250 (64%) known-onset morning strokes. No difference in baseline characteristics, stroke severity, stroke etiology, neurologic deterioration, discharge disposition or functional outcome was detected. Known-onset morning stroke patients were significantly more likely to get thrombolytic therapy and have higher risk of in-hospital mortality. Wake-up stroke patients tended to be older, have higher diastolic blood pressure and have longer length of hospital stay. DISCUSSION: While patients with wake-up stroke were similar to patients with known-onset morning stroke in many respects, patients with known onset morning stroke were significantly more likely to get treated with thrombolytic therapy and have higher in-hospital mortality.

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.