Sparing the hippocampus and the hypothalamic- pituitary region during whole brain radiotherapy: a volumetric modulated arc therapy planning study.

BACKGROUND: Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. INTRODUCTION: Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. METHODS: Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. RESULTS: The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI). CONCLUSION: Simultaneous dose reduction to the hippocampus and the HT-P area did not compromise the PTV coverage in patients undergoing WBRT+SIB or PCI using VMAT. While the feasibility of the presented approach is promising, prospective neurologic, endocrine outcome and safety studies are required.

Are hypothalamic- pituitary (HP) axis deficiencies after whole brain radiotherapy (WBRT) of relevance for adult cancer patients? - a systematic review of the literature.

BACKGROUND: Cranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients. METHODS: A systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis. RESULTS: Twenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed. CONCLUSION: Hypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.

Radiotherapy for prostate cancer: DISCERN quality assessment of patient-oriented websites in 2018.

BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in men. Radiotherapy represents one major treatment option in different therapeutic settings. As patients increasingly rely on internet-based medical information, we examined the quality of information on radiotherapy and prostate cancer in websites used by laypersons. METHODS: An Internet search from a patients` perspective was carried out using different search engines (Google, Yahoo and Bing, search terms: "prostate cancer" and "radiotherapy"). The quality of search results was analyzed with regard to the DISCERN score, HON code certification, the JAMA criteria and the ALEXA traffic rank. RESULTS: In general, websites were of good quality. The highest quality was found for websites operated by charity organizations. No significant differences in results obtained via the above-mentioned tools were seen for the examined search engines, but Google revealed the most stable search results in terms of temporal changes. CONCLUSION: Patients with prostate cancer can sufficiently inform themselves on general treatment options including radiotherapy on websites directed at laypersons. However, no simple strategy could identify high quality websites in general. For treating physicians, it is important to support patients in interpreting and ranking the vast quantity of information.

Side effects of radiotherapy in breast cancer patients : The Internet as an information source.

AIM: Breast cancer is the most common cancer type among women necessitating adjuvant radiotherapy. As the Internet has become a major source of information for cancer patients, this study aimed to evaluate the quality of websites giving information on side effects of radiotherapy for breast cancer patients. METHODS: A patients' search for the English terms "breast cancer - radiotherapy - side effects" and the corresponding German terms "Brustkrebs - Strahlentherapie - Nebenwirkungen" was carried out twice (5 months apart) using the search engine Google. The first 30 search results each were evaluated using the validated 16-question DISCERN Plus instrument, the Health on the Net Code of Conduct (HONcode) certification and the Journal of the American Medical Association (JAMA) benchmark criteria. The overall quality (DISCERN score) of the retrieved websites was further compared to queries via Bing and Yahoo search engines. RESULTS: The DISCERN score showed a great range, with the majority of websites ranking fair to poor. Significantly superior results were found for English websites, particularly for webpages run by hospitals/universities and nongovernmental organizations (NGO), when compared to the respective German categories. In general, only a minority of websites met all JAMA benchmarks and was HONcode certified (both languages). We did not determine a relevant temporal change in website ranking among the top ten search hits, while significant variation occurred thereafter. Mean overall DISCERN score was similar between the various search engines. CONCLUSION: The Internet can give breast cancer patients seeking information on side effects of radiotherapy an overview. However, based on the currently low overall quality of websites and the lack of transparency for the average layperson, we emphasize the value of personal contact with the treating radio-oncologist in order to integrate and interpret the information found online.

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 (

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.

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.

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.

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.

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.

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.

DIFFERENTIAL TREATMENT EFFECTS OF STANDARD AND HYPOFRACTIONATED RADIATION REGIMENS IN GLIOBLASTOMA PATIENTS.

BACKGROUND: The identification of the subgroups with differential treatment effects (DTE) is important for decisionmaking in personalized treatment. The DTE analysis assists in identifying patients who are more likely to benefit from a particular treatment regimen. The aim of the study was to analyze DTE in terms of the survival of glioblastoma (GBM) patients in the groups of standard radiotherapy (SRT) and hypofractionated radiotherapy (HRT) by the multicluster modeling of homogenous groups while retaining the statistical characteristics of the overall primary study cohort. PATIENTS AND METHODS: The cohort of 159 patients with newly diagnosed GBM stratified according to the radiotherapy regimen (HRT group (n = 110/69.2%); SRT group (n = 49/30.8%)) was evaluated retrospectively. Forty-eight subgroups (multiclusters) were created by enumerating all possible combinations of 5 significant covariates (age, sex, the radicality of the surgical resection, chemotherapy, and Karnofsky performance status) of the Cox model. The DTE for the cancerspecific survival (CSS) within 48 modeled multiclusters were studied by comparing the interpolated Weibull CSS curves according to the Kolmogorov - Smirnov test. RESULTS: The findings showed that the SRT group was superior to the HRT group by CSS only in 3 of the modeled clusters presenting clinical scenarios with a non-radical tumor resection, no chemotherapy, and low Karnofsky functional status (≤ 70 scores) (Cluster 10: male aged < 60; Cluster 21: female aged ≥ 60; Cluster 22: male aged ≥ 60). Most of the studied clinical variants (45 of 48 multiclusters) did not demonstrate a significant difference when comparing the interpolated Weibull curves of the CSS for the SRT and HRT groups according to the Kolmogorov - Smirnov test (p ≥ 0.05). CONCLUSIONS: We propose a novel multicluster modeling approach that addresses DTE in relatively small samples of GBM patients receiving SRT or HRT. This original analytical method can be taken into consideration while designing new well-powered prospective trials aimed at the subgroup analysis in GBM patients who will be most beneficial from personalized treatment strategies.

Evaluation of ocular and systemic endpoints after radiation of posterior uveal melanoma - A systematic review and meta-analysis.

Background: Due to the large number of radiotherapeutic options for treatment of posterior uveal melanoma (UM), advantages of each option regarding important clinical endpoints have yet to be determined. Therefore, objective of this systematic review was to analyze the numerous pro- and retrospective cohort studies focusing on the efficacy of different radiotherapeutic options for UM in adults, considering local tumor control, overall survival, visual acuity, eye preservation, metastasis, radiation side effects and dose rates. Methods: The Review was performed based on the Cochrane Handbook of Systematic Reviews. The PubMed database was searched for studies published from January 1st, 2000, up to December 31st, 2021. Research, study selection and critical appraisal was performed by two reviewers. The risk of bias assessment was performed through the revised Cochrane risk of bias tools RoB 2 and ROBINS-I. A meta-analysis of proportions was performed using R (R version 4.1.3, library: meta, procedure: metaprop). This systematic review was registered with Prospero (ID CRD42022311758). Results: Of 4886 studies identified in the database, a total of 20 studies with 4979 participants were included in the qualitative synthesis. Through critical appraisal with ROBINS-I and RoB 2, studies received a 'moderate', 'serious' or 'some concerns' overall risk of bias. Heterogeneity analysis allowed for meta-analysis of proportion of 3 outcome-therapy combinations: local tumor control with I-125 Brachytherapy (proportion: 0.94, CI 95 %: 0.91-0.98), local tumor control with proton therapy (proportion: 0.96, CI 95 %: 0.92-1.00) and eye preservation with I-125 brachytherapy (proportion: 0.91, CI 95 %: 0.88-0.93). This shows local tumor control to be at 94 % with I-125 brachytherapy and at 96 % with proton therapy, as well as an eye preservation rate of 91 % with I-125 brachytherapy. Discussion: The evaluation of outcomes of radiotherapy in UM is limited because of missing data on radiation doses as well as great heterogeneity of study protocols. Radiation therapy outcomes are so far not comparable. Therefore, we recommend for upcoming studies on this topic to provide the biological effective dose (BED) or the equivalent dose in 2 Gy fractions (EQD2) per eye structure, thereby enabling a comparison of outcomes of different forms of radiation therapy.

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.

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.

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.

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.

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.