Melatonin exhibits partial protective effects against gemcitabine- and cisplatin-induced kidney and reproductive injuries in mice.

Cisplatin has the potential to cause kidney and reproductive organ injuries, prompting the search for protective agents against cisplatin-induced toxicity. Melatonin, an antioxidant hormone, has shown promise in mitigating oxidative stress in various organs. However, its protective effects on cisplatin-induced kidney and reproductive injuries have not been extensively investigated. The aim of this study was to explore the potential protective effects of melatonin on cisplatin-induced kidney and reproductive injuries when administered in combination with gemcitabine in mice. Male C57BL/6 mice were subjected to a seven-week treatment with gemcitabine plus cisplatin, with or without melatonin intervention. The testis, epididymis, and kidney were assessed through histological analysis and measurement of blood parameters. Treatment with cisplatin led to a significant reduction in testicular weight, histological abnormalities, and alterations in reproductive hormone levels. Melatonin exhibited a slight protective effect on the testis, with higher doses of melatonin yielding better outcomes. However, melatonin did not reverse the effects of cisplatin on the epididymis. Administration of melatonin before and during treatment with cisplatin plus gemcitabine in mice demonstrated a modest protective effect on testicular injuries, while showing limited effects on epididymal injuries. Serum creatinine levels in the group treated with gemcitabine plus cisplatin treatment and high-dose melatonin approached those of the control group, indicating a protective effect on the kidney. These findings underscore the potential of melatonin as a protective agent against cisplatin-induced kidney and reproductive injuries and emphasize the need for further research to optimize its dosage and evaluate its long-term effects.

Using deep learning models to analyze the cerebral edema complication caused by radiotherapy in patients with intracranial tumor.

Using deep learning models to analyze patients with intracranial tumors, to study the image segmentation and standard results by clinical depiction complications of cerebral edema after receiving radiotherapy. In this study, patients with intracranial tumors receiving computer knife (CyberKnife M6) stereotactic radiosurgery were followed using the treatment planning system (MultiPlan 5.1.3) to obtain before-treatment and four-month follow-up images of patients. The TensorFlow platform was used as the core architecture for training neural networks. Supervised learning was used to build labels for the cerebral edema dataset by using Mask region-based convolutional neural networks (R-CNN), and region growing algorithms. The three evaluation coefficients DICE, Jaccard (intersection over union, IoU), and volumetric overlap error (VOE) were used to analyze and calculate the algorithms in the image collection for cerebral edema image segmentation and the standard as described by the oncologists. When DICE and IoU indices were 1, and the VOE index was 0, the results were identical to those described by the clinician.The study found using the Mask R-CNN model in the segmentation of cerebral edema, the DICE index was 0.88, the IoU index was 0.79, and the VOE index was 2.0. The DICE, IoU, and VOE indices using region growing were 0.77, 0.64, and 3.2, respectively. Using the evaluated index, the Mask R-CNN model had the best segmentation effect. This method can be implemented in the clinical workflow in the future to achieve good complication segmentation and provide clinical evaluation and guidance suggestions.

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvß3 Axis.

Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvß3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and ß3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvß3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvß3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvß3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.

Concurrent Sorafenib and Radiotherapy versus Radiotherapy Alone for Locally Advanced Hepatocellular Carcinoma: A Propensity-Matched Analysis.

PURPOSE: Evidence is lacking concerning the benefit of the combination of sorafenib and radiotherapy to treat advanced hepatocellular carcinoma (HCC). To date, no publication has reported the outcomes of radiotherapy alone versus concurrent therapy. We aimed to compare the effectiveness of radiotherapy alone versus concurrent radiotherapy and sorafenib for locally advanced hepatocellular carcinoma. MATERIALS AND METHODS: We conducted a propensity score matching (PSM) cohort study comparing the effectiveness of the concurrent use of sorafenib and external beam radiotherapy versus radiotherapy alone in Barcelona Clinic Liver Cancer (BCLC) stage B or C, nonsurgically managed, nonmetastatic patients with HCC. Two subpopulations were matched based on baseline characteristics. Stratified analysis was also performed to assess the heterogeneous effects of the two arms. Overall survival (OS) was compared. Radiation-induced liver disease (RILD) and overt gastrointestinal (GI) bleeding events were also recorded. RESULTS: Seven hundred thirty-one BCLC stage B or C nonmetastatic HCC patients were identified from 2007 to 2017. Of these, 347 patients met the inclusion criteria (Radiotherapy alone: 269 patients; concurrent therapy: 78 patients). Propensity score matching yielded 73 patients each in the radiotherapy and concurrent groups. The median OS was 9.6 months in the radiotherapy-alone group and 9.9 months in the concurrent group (hazard ratio (HR): 1.12; 95% CI=0.78-1.62; p=0.544). Posttreatment toxicities, including radiation-induced liver disease and overt gastrointestinal bleeding, showed no significant differences between the groups. CONCLUSION: In our study, the concurrent use of sorafenib and conventional external beam radiotherapy shows no survival benefit over radiotherapy alone for locally advanced hepatocellular carcinoma.

Proton versus photon radiotherapy for primary hepatocellular carcinoma: a propensity-matched analysis.

BACKGROUND: Proton radiotherapy has a dosimetric advantage over photon radiotherapy. Many retrospective studies have shown promising results with proton radiotherapy in treating hepatocellular carcinoma (HCC). However, clinical evidence demonstrating the benefit of protons over photons is still limited. We therefore compared the clinical outcomes of the two modalities using medical research databases from our medical foundation. METHODS: We conducted a propensity score-matched cohort study based on our multi-institution medical organization research database. From January 2007 to January 2018, a total of 413 patients (photon: 349; proton: 64) who were diagnosed with HCC and primarily treated with radiotherapy with curative intent were enrolled. Overall survival (OS) and radiation-induced liver disease (RILD) were assessed. Stratified analysis was also performed to evaluate the heterogeneous effects of the two arms. RESULTS: A total of 110 patients (photon: 55; proton: 55) were analyzed in the propensity-matched series. The matched groups were balanced for baseline tumor risk factors. Cox regression analysis revealed a significant survival benefit in the proton group (p = 0.032, HR 0.56, 95% CI 0.33-0.96). The median overall survival in the proton group was not reached and that in the photon group was 17.4 months. The biological equivalent dose of radiotherapy was significantly higher in the proton group than in the photon group (median, 96.56 Gray [relative biological effectiveness] vs. 62.5 Gray, p < 0.001). The risk of RILD was significantly lower in the proton group (11.8% vs. 36%, p = 0.004). CONCLUSIONS: Proton radiotherapy could deliver a higher radiation dose than photon radiotherapy without increasing the risk of RILD and result in a better overall survival rate for those diagnosed with HCC and treated with radiotherapy with curative intent.

Gender Is a Significant Prognostic Factor for Upper Tract Urothelial Carcinoma: A Large Hospital-Based Cancer Registry Study in an Endemic Area.

Introduction: Our hospital is a tertiary medical center located in southern Taiwan, which is an endemic area for upper tract urothelial carcinoma (UTUC) cases. Using a large registry-based surgical database, we examined our cohort of patients with UTUC, and evaluated the treatment outcome and gender-specific differences in this population. Methods: A total of 506 patients with localized UTUC undergoing nephroureterectomy from 2004 to 2013 were enrolled. The patient, tumor, and treatment-related characteristics were prospectively recorded by the registry. Overall (OS) and cancer-specific (CSS) survival outcomes were evaluated as well. Gender differences as related to clinical and pathological factors were examined by chi-square testing. Univariate and multivariate Cox regression analyses were applied. Results: There were more female patients (57.9%) in this population. The median follow-up was 6.9 years for living patients. The actuarial 5-year OS and CSS rates were 69.4 and 84.9%, respectively. Being female, aged <70 years, and early T-stage were statistically significantly associated with better OS and CSS by multivariate analyses. The 5-year CSS rates for females vs. males were 89.6 and 78.5%, respectively (P < 0.005). A subgroup analysis suggested that better survival outcomes for females only existed in the stage 0a/0is/I (non-muscle-invasive), but not in the advanced stage. Conclusions: In an endemic area, females were more likely diagnosed with UTUC, but had significantly improved OS and CSS compared to their male counterparts, which were mostly driven by the non-muscle-invasive cases. Future research should focus on better understanding the epidemiologic risk-factor profile and pathophysiologic differences based on gender.

Analysis of prognostic factors and clinical outcomes in uterine cervical carcinoma with isolated para-aortic lymph node recurrence.

To evaluate clinical outcomes and to identify prognostic factors in isolated para-aortic lymph node (PALN) recurrence, we retrospectively reviewed 65 patients who developed PALN recurrence as the first site of tumor progression from a total of 1521 patients who were treated with curative pelvic radiation therapy (RT) for uterine cervical carcinoma between May 1993 and January 2017. Forty-five of the 65 patients received salvage therapy. The median salvage PALN radiation dose was 54 Gy (range: 18 to 62 Gy). Prognostic factors for overall survival (OS) and distant metastases (DMs) were analyzed with univariate and multivariate Cox regression. The median follow-up period for surviving patients was 61 months (4-202 months). The median OS was 27.7 months (0.3-202 months). The highest level of PALN metastases at or above the L1 spinal level (hazard ratio [HR] 9.88, 95% confidence interval [CI] 3.44-28.38, P<0.001) and the presence of leg edema and/or back pain at recurrence (HR 3.25, 95% CI 1.57-6.75, P=0.002) were significantly associated with worse OS. A significantly higher incidence of DMs (HR 5.97, 95% CI 2.05-17.35, P=0.001) was found in the patients with a high level (≥L1) of PALN metastases. Salvage RT (HR 0.35, 95% CI 0.17-0.71, P=0.004) and restaging with positron emission tomography/computed tomography (PET/CT) (HR 0.2, 95% CI 0.04-0.93, P=0.039) were independent predictors of a better OS. In conclusion, a high level (≥L1) of PALN metastases predicts poor survival and a high rate of DMs. Periodic surveillance for early detection and restaging by PET/CT imaging to identify the optimal treatment at recurrence is recommended.

Pretreatment prognostic factors of survival and late toxicities for patients with nasopharyngeal carcinoma treated by simultaneous integrated boost intensity-modulated radiotherapy.

BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS). RESULTS: Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2-3 vs. N0-1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3-4 (HR: 3.5, 95% CI: 1.0-12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001-1.011, p = 0.027) were associated with higher incidence of radiation neuropathy. CONCLUSION: N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.

Carcinoembryonic antigen as a marker of radioresistance in colorectal cancer: a potential role of macrophages.

BACKGROUND: We sought to identify the carcinoembryonic antigen (CEA) as a marker of radioresistance in rectal cancer. METHODS: From July 1997 to January 2008, 104 patients with stage II or III rectal cancer who were treated with post-operative radiotherapy (PORT) were included in this study. The doses of radiotherapy ranged from 45 to 54.6 Gy. The CEA levels were measured before surgery. We analyzed the actuarial rates of overall survival (OS), distant metastasis (DM), and local recurrence (LR) using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. We used THP-1 monocyte cell lines for macrophage differentiation (M0, M1 or M2). The RNA extracted from the macrophages was analyzed via a genomic method in the core laboratory. The radiosensitivities of CEA-rich LS1034 cells were compared between cells with and without the conditioned media from CEA-stimulated macrophages. RESULTS: Preoperative CEA levels ≥10 ng/mL were independent predictive factors for OS (p = 0.005), DM (p = 0.026), and LR (p = 0.004). The OS rates among the patients with pretreatment CEA levels < 10 ng/mL and ≥10 ng/mL were 64.5% and 35.9% (p = 0.004), respectively. The corresponding rates of DM were 40.6% and 73.1% (p = 0.024). The corresponding rates of LR were 6.6% and 33.9% (p = 0.002). In the M0 macrophages, exogenous CEA elicited a dose-response relationship with M2 differentiation. In the CEA-stimulated M0 cells, some mRNAs were upregulated by as much as 5-fold, including MMP12, GDF15, and JAG1. In the CEA-stimulated M2 cells, a 4-fold up-regulation of GADD45G mRNA was noted. The conditioned media from the CEA-stimulated M2 cells elicited an increase in the numbers of LS180, SW620, and LS1034 cells after irradiation. CEA caused the M2 differentiation of the macrophages. CONCLUSION: Pretreatment CEA levels ≥10 ng/mL are a significant risk factor for OS, DM, and LR following PORT for rectal cancer. CEA causes radioresistance in the presence of M2 macrophages. More comprehensive examinations prior to surgery and intensive adjuvant therapy are suggested for patients with CEA levels ≥10 ng/mL. Further studies of these mechanisms are needed.

Radiation-induced secondary malignancies for nasopharyngeal carcinoma: a pilot study of patients treated via IMRT or VMAT.

BACKGROUND: Patients treated with radiotherapy are at risk of developing a second cancer during their lifetime, which can directly impact treatment decision-making and patient management. The aim of this study was to qualify and compare the secondary cancer risk (SCR) after intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: We analyzed the treatment plans of a cohort of 10 NPC patients originally treated with IMRT or VMAT. Dose distributions in these plans were used to calculate the organ equivalent dose (OED) with Schneider's full model. Analyses were applied to the brain stem, spinal cord, oral cavity, pharynx, parotid glands, lung, mandible, healthy tissue, and planning target volume. RESULTS: We observed that the OED-based risks of SCR were slightly higher for the oral cavity and mandible when VMAT was used. No significant difference was found in terms of the doses to other organs, including the brain stem, parotids, pharynx, submandibular gland, lung, spinal cord, and healthy tissue. In the NPC cohort, the lungs were the organs that were most sensitive to radiation-induced cancer. CONCLUSION: VMAT afforded superior results in terms of organ-at-risk-sparing compared with IMRT. Most OED-based second cancer risks for various organs were similar when VMAT and IMRT were employed, but the risks for the oral cavity and mandible were slightly higher when VMAT was used.

Therapeutic outcome of nasopharyngeal carcinoma with cranial nerve palsy: a single institution experience of 104 patients.

PURPOSE: Cranial nerve (CN) palsy is the main symptom in patients with locally advanced nasopharyngeal carcinoma (NPC). This study aimed to evaluate the therapeutic outcome of NPC with CN palsy and to analyze the prognostic factors. PATIENTS AND METHODS: A total of 104 NPC patients with CN palsy curatively treated by conventional (n=44) or conformal (n=60) radiotherapy (RT) were enrolled. Upper CN palsy was present in 81 patients, lower CN palsy in four patients, and both upper and lower CN palsy in 19 patients. Forty-one patients had CN palsy for >2 months before diagnosis. RESULTS: Complete recovery of CN palsy was observed in 74 patients. The actuarial 5-year locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 58.2%, 62.2%, and 38.4%, respectively. No significant difference was observed in CN recovery, LRC, DMFS, or OS for patients treated by conventional versus conformal technique. However, significant reduction of grade 3 or greater toxicities was found in those treated by the conformal technique (odds ratio =0.28). CONCLUSION: Patients with CN palsy presenting >2 months before diagnosis were hard to recover from palsy. The LRC, OS, and recovery from CN palsy did not significantly change with the treatment evolution. Patients with complete recovery from CN palsy had longer OS.

Differences in the outcomes and complications between elderly and younger uterine cervical cancer patients treated by definitive radiotherapy - A propensity score-matched study.

PURPOSE: To evaluate the differences in the treatment outcomes and complications between elderly patients and younger patients with uterine cervical cancer (CxCa). METHODS AND MATERIALS: From April 1993 to December 2007, 138 CxCa patients aged ≥75years (Elderly group) and 334 CxCa patients aged <60years (Young group) who underwent definitive radiotherapy/chemoradiotherapy at our institution were reviewed. Two propensity score-matched cohorts of patients were selected from both age groups to evaluate the differences in the outcomes and complications. The overall survival (OS), cancer-specific survival (CSS), local failure (LF), distant failure (DF), late proctitis, and cystitis were compared between the age groups. RESULTS: The median follow-up time for survivors was 60.6months. A cohort of 99 pairs of patients was selected for the outcome comparison; there was a significant difference in the 5-year OS between the Elderly and Young groups (49.2% and 71.5%, respectively; p<0.001) but no differences in CSS, LF, and DF. Another cohort of 79 pairs of patients was selected for complication analysis. Significant differences between the Elderly and Young groups were observed in the 5-year cumulative grade 2 proctitis (39.7% and 17.2%, respectively; p=0.015) and grade 3 proctitis (18.1% and 6.2%, respectively; p=0.040). CONCLUSIONS: Although OS was worse in the elderly patients, no differences were observed in CSS, LF, and DF. Meanwhile, elderly patients tended to have higher radiation-related proctitis than younger patients. A more conservative treatment strategy for elderly CxCa patients is reasonable in our future practice.

Prognostic factors associated with radiotherapy for cervical cancer with computed tomography-detected para-aortic lymph node metastasis.

Patients with cervical cancer diagnosed with a para-aortic lymph node (PALN) metastasis by computed tomography (CT) scan were analyzed to identify associated prognostic factors. A total of 55 patients were reviewed, and 27 of these patients underwent extended-field radiotherapy (EFRT). The median PALN dose in patients receiving EFRT was 45 Gy (range, 27-57.6 Gy). Of the 55 patients, 28 underwent pelvic radiotherapy (RT); concurrent chemoradiotherapy (CCRT) was administered to 41 patients. The Kaplan-Meier method was used to calculate the actuarial rate. Multivariate analysis was performed using the Cox proportional hazards model. Five-year overall survival (OS) rates were 41% and 17.9% in patients undergoing EFRT and pelvic RT (P = 0.030), respectively. Age < 53 years (P = 0.023), FIGO Stage I-II (P = 0.002), and treatment with EFRT (P = 0.003) were independent predictors of better OS. The use of CCRT (P = 0.014), Stage I-II (P = 0.002), and treatment using EFRT (P = 0.036) were independent predictors of distant metastasis. In patients undergoing EFRT plus CCRT, the 5-year OS was 50%. Three-year PALN disease-free rates were 8.8%, 57.9% and 100% (P < 0.001) in CCRT patients who received PALN doses of 0 Gy, ≤45 Gy and ≥50.4 Gy, respectively. Although PALN metastasis is thought to be distant metastasis in cervical cancer, EFRT plus CCRT shows a good outcome, particularly in younger patients in an early FIGO stage. Cervical cancer with a PALN metastasis should not be considered incurable. Doses ≥50.4 Gy for treating PALN may result in better disease control.

Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND: Vascular abnormalities are the predominant histologic changes associated with radiation in nasopharyngeal carcinoma (NPC). This study examined if the duration after radiotherapy correlates with the progression of carotid intima-media thickness (IMT) and investigated its relationship with inflammatory markers. METHODS: One hundred and five NPC patients post-radiotherapy for more than one year and 25 healthy control subjects were examined by B-mode ultrasound for IMT measurement at the far wall of the common carotid artery (CCA). Surrogate markers including lipid profile, HbA1c, and high sensitive C-reactive protein (hs-CRP) were assessed. RESULTS: The IMT of CCA was significantly increased in NPC patients and carotid plaque was detected in 38 NPC patients (38/105, 36.2%). Significant risk factors for carotid plaques included age, duration after radiotherapy, and HbA1c levels. Age, duration after radiotherapy, hs-CRP, HbA1c, and platelet count positively correlated with IMT. The cut-off value of age and duration after radiotherapy for the presence of plaque was 52.5 years and 42.5 months, respectively. In NPC subjects, multiple linear regression analysis revealed that age, gender, duration after radiotherapy and platelet counts were independently associated with CCA IMT. After adjustments for age, gender and platelet counts, IMT increased in a linear manner with duration after radiotherapy. CONCLUSIONS: Radiation-induced vasculopathy is a dynamic and progressive process due to late radiation effects. Extra-cranial color-coded duplex sonography can be part of routine follow-up in NPC patients aged ≥50 years at 40 months post-radiotherapy.

Long-term effects of neck irradiation on cardiovascular autonomic function: a study in nasopharyngeal carcinoma patients after radiotherapy.

INTRODUCTION: Baroreflex failure has been reported as a late sequalum of neck radiotherapy. In this study we investigated cardiovascular autonomic function in patients after neck radiotherapy to determine predictive factors associated with outcome. METHODS: Eighty-nine patients with nasopharyngeal carcinoma were evaluated ≥6 months after radiotherapy for cardiovascular autonomic function and compared with 48 control subjects. Inflammatory markers and carotid intima-media thickness were also assessed. RESULTS: Autonomic parameters of heart rate response to deep breathing and Valsalva ratio were significantly lower in the patient group. Cardiovascular autonomic impairment was generally mild with relative sparing of the efferent cardiovagal pathway. By univariate and multivariate analyses, the time after radiotherapy and C-reactive protein level were significantly associated with the degree of cardiovascular autonomic dysfunction. CONCLUSIONS: Radiation-induced cardiovascular autonomic impairment is a dynamic and progressive process that occurs long after radiotherapy. Chronic inflammation plays a major role in this process.

Surgical resection improves the survival of selected hepatocellular carcinoma patients in Barcelona clinic liver cancer stage C.

BACKGROUND: Sorafenib is the only approved agent recommended by the American Association Study of Liver Disease guidelines for hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C. AIMS: To calculate and compare overall survival rates in hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C treated with various therapies or supportive care alone. METHODS: This was a retrospective study, in which medical data from 411 newly diagnosed hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C and Child-Pugh class A were analyzed and compared. RESULTS: Eighty-eight patients were treated with supportive care and 323 were treated with surgical resection (68/323, 21.1%), local ablation therapy (8/323, 2.5%), transarterial embolization (140/323, 43.3%), systemic chemotherapy or radiotherapy (96/323, 29.7%), and sorafenib (11/323, 3.4%). Median survival was 11 months (95% confidence interval, 9.0-13.1) in treated patients compared with 3.9 months in the supportive care group (hazard ratio, 0.45; 95% confidence interval, 0.35-0.59; p<0.001). Patients who underwent surgical resection had the longest survival compared to patients undergoing other treatments (33.4 months versus 8.1 months, p<0.001). CONCLUSIONS: Surgical resection resulted in excellent outcomes. Although sorafenib is currently recommended, oncologists should endeavour to select optimal candidates for surgical resection to gain more survival benefit.

Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments.

BACKGROUND: With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman-Kutcher-Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. METHODS: Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson's chi-squared test, Nagelkerke's R2, the area under the receiver operating characteristic curve, and the Hosmer-Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson's chi-squared test was used to test the goodness of fit and association. RESULTS: Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50) and the slope of the dose-response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. CONCLUSIONS: Our study shows the agreement between the NTCP parameter modeling based on SEF and QoL data, which gave a NPV of 100% with each dataset, and the QUANTEC guidelines, thus validating the cut-off values of 20 and 25 Gy. Based on these results, we believe that the QUANTEC 25/20-Gy spared-gland mean-dose guidelines are clinically useful for avoiding xerostomia in the HN cohort.

Concurrent metastatic thymic carcinoma and postirradiation sarcoma.

We present a case of concurrent metastatic thymic carcinoma and postirradiation sarcoma in the same lobe of the lung in a woman who had received partial resection of thymic carcinoma with chemoradiotherapy 11 years ago. One tumor showed similar histology to the previous carcinoma. The other tumor was a pleomorphic sarcoma, suggestive of a postirradiation sarcoma. Irradiation-induced sarcomas are rare and have not been reported in patients with thymic carcinoma. This case may serve as a model in considering the possibility of postirradiation sarcoma for patients encountering recurrent masses with the history of radiotherapy for thymic carcinoma several years ago.

Pretreatment carcinoembryonic antigen level is a risk factor for para-aortic lymph node recurrence in addition to squamous cell carcinoma antigen following definitive concurrent chemoradiotherapy for squamous cell carcinoma of the uterine cervix.

BACKGROUND: To identify pretreatment carcinoembryonic antigen (CEA) levels as a risk factor for para-aortic lymph node (PALN) recurrence following concurrent chemoradiotherapy (CCRT) for cervical cancer. METHODS: From March 1995 to January 2008, 188 patients with squamous cell carcinoma (SCC) of the uterine cervix were analyzed retrospectively. No patient received PALN irradiation as the initial treatment. CEA and squamous cell carcinoma antigen (SCC-Ag) were measured before and after radiotherapy. PALN recurrence was detected by computer tomography (CT) scans. We analyzed the actuarial rates of PALN recurrence by using Kaplan-Meier curves. Multivariate analyses were carried out with Cox regression models. We stratified the risk groups based on the hazard ratios (HR). RESULTS: Both pretreatment CEA levels ≥ 10 ng/mL and SCC-Ag levels < 10 ng/mL (p < 0.001, HR = 8.838), SCC-Ag levels ≥ 40 ng/mL (p < 0.001, HR = 12.551), and SCC-Ag levels of 10-40 ng/mL (p < 0.001, HR = 4.2464) were significant factors for PALN recurrence. The corresponding 5-year PALN recurrence rates were 51.5%, 84.8%, and 27.5%, respectively. The 5-year PALN recurrence rate for patients with both low (< 10 ng/mL) SCC and CEA was only 9.6%. CEA levels ≥ 10 ng/mL or SCC-Ag levels ≥ 10 ng/mL at PALN recurrence were associated with overall survival after an isolated PALN recurrence. Pretreatment CEA levels ≥ 10 ng/mL were also associated with survival after an isolated PALN recurrence. CONCLUSIONS: Pretreatment CEA ≥ 10 ng/mL is an additional risk factor of PALN relapse following definitive CCRT for SCC of the uterine cervix in patients with pretreatment SCC-Ag levels < 10 ng/mL. More comprehensive examinations before CCRT and intensive follow-up schedules are suggested for early detection and salvage in patients with SCC-Ag or CEA levels ≥ 10 ng/mL.

Postoperative low pelvic radiotherapy and chemotherapy for stage II and III rectal cancer.

OBJECTIVES: To evaluate whether postoperative low pelvic radiotherapy (RT) combined with chemotherapy is an appropriate treatment for stage II and III rectal cancer. METHODS: Between November 1997 and May 2006, 104 patients with stage II and III rectal cancer underwent surgery as the primary treatment followed by postoperative RT combined with chemotherapy in our institute and were reviewed retrospectively. Sixty-nine patients received low pelvic RT only (upper margin at 1 cm above the low end of the sacroiliac joint; median dose 54 Gy) (low pelvic RT group) and the other 35 patients received whole pelvic RT (upper margin at the mid L5; median dose 43.2 Gy) and subsequently received a boost to the low pelvis (total median dose 54 Gy) (whole pelvic RT group). RESULTS: The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 72% versus 63%, 86% versus 84%, and 66% versus 62% for low pelvic versus whole pelvic RT group. There were no statistical differences in these 2 groups. Two patients (2.9%) of the low pelvic RT group and 2 patients (5.7%) of the whole pelvic RT group developed upper pelvis relapse, which was out of the low pelvic field. The incidence of Grade 3 to 5 small bowel late complications of the low pelvic RT group was significantly less than that of the whole pelvic RT group (4.3% vs. 20%) (P=0.029). CONCLUSIONS: Low pelvic RT significantly reduces small bowel late complications and does not compromise the overall survival rate, local control rate, and distant metastasis-free rate.