Chaosu Hu

RADIATION-INDUCED CRANIAL NERVE PALSY: A CROSS-SECTIONAL STUDY OF NASOPHARYNGEAL CANCER PATIENTS AFTER DEFINITIVE RADIOTHERAPY

PURPOSE To address the characteristics and the causative factors of radiation-induced cranial nerve palsy (CNP) in nasopharyngeal carcinoma (NPC) patients with an extensive period of followed-up. PATIENTS AND METHODS A total of 317 consecutive and nonselected patients treated with definitive external-beam radiotherapy between November 1962 and February 1995 participated in this study. The median doses to the nasopharynx and upper neck were 71 Gy (range, 55-86 Gy) and 61 Gy (range, 34-72 Gy), respectively. Conventional fractionation was used in 287 patients (90.5%). Forty-five patients (14.2%) received chemotherapy. RESULTS The median follow-up was 11.4 years (range, 5.1-38.0 years). Ninety-eight patients (30.9%) developed CNP, with a median latent period of 7.6 years (range, 0.3-34 years). Patients had a higher rate of CNP (81 cases, 25.5%) in lower-group cranial nerves compared with upper group (44 cases, 13.9%) (χ(2) = 34.444, p < 0.001). Fifty-nine cases experienced CNP in more than one cranial nerve. Twenty-two of 27 cases (68.8%) of intragroup CNP and 11 of 32 cases (40.7%) of intergroup CNP occurred synchronously (χ(2) = 4.661, p = 0.031). The cumulative incidences of CNP were 10.4%, 22.4%, 35.5%, and 44.5% at 5, 10, 15, and 20 years, respectively. Multivariate analyses revealed that CNP at diagnosis, chemotherapy, total radiation dose to the nasopharynx, and upper neck fibrosis were independent risk factors for developing radiation-induced CNP. CONCLUSION Radiation-induced fibrosis may play an important role in radiation-induced CNP. The incidence of CNP after definitive radiotherapy for NPC remains high after long-term follow-up and is dose and fractionation dependent.

Is elective irradiation to the lower neck necessary for N0 nasopharyngeal carcinoma

PURPOSE To summarize our experience and treatment results in lymph node-negative nasopharyngeal carcinoma treated in a single institution. METHODS AND MATERIALS From January 2000 to December 2003, 410 patients with lymph node-negative nasopharyngeal carcinoma were retrospectively analyzed. The T-stage distribution was 18.8% in T1, 54.6% in T2 (T2a, 41 patients; T2b, 183 patients), 13.2% in T3, and 13.4% in T4. All patients received radiotherapy to the nasopharynx, skull base, and upper neck drainage areas, including levels II, III, and VA. The dose was 64-74 Gy, 1. 8-2.0 Gy per fraction over 6.5-7.5 weeks to the primary tumor with (60)Co or 6-MV X-rays, and 50-56 Gy to levels II, III, and VA. Residual disease was boosted with either (192)Ir afterloading brachytherapy or small external beam fields. RESULTS The median follow-up time was 54 months (range, 3-90 months). Four patients developed neck recurrence, and only 1 patient (0.2%) experienced relapse outside the irradiation fields. The 5-year overall survival rate was 84.2%. The 5-year relapse-free survival rate, distant metastasis-free survival rate, and disease-free survival rate were 88.6%, 90.6% and 80.1%, respectively. Both univariate and multivariate analyses demonstrated that T classification was the only significant prognostic factor for predicting overall survival. The observed serious late toxicities were radiation-induced brain damage (7 cases), cranial nerve palsy (16 cases), and severe trismus (13 cases; the distance between the incisors was < or = 1 cm). CONCLUSION Elective levels II, III, and VA irradiation is suitable for nasopharyngeal carcinoma without neck lymph node metastasis.

The risk of second primary tumors in patients with nasopharyngeal carcinoma after definitive radiotherapy.

Second primary tumors (SPTs) have a substantial impact on survival in cancer patients. However, risk factors for SPTs have not been documented well, especially in nasopharyngeal carcinoma (NPC). The objective of this retrospective analysis was to evaluate such risks in patients with NPC after they received definitive radiation treatment.

Neoadjuvant chemotherapy followed by concurrent chemoradiation for locoregionally advanced nasopharyngeal carcinoma: Interim results from 2 prospective phase 2 clinical trials

The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5‐fluorouracil (5‐FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA/IVB nasopharyngeal cancer (NPC).

Prognostic Impact of Primary Tumor Volume in Patients With Nasopharyngeal Carcinoma Treated by Definitive Radiation Therapy

Objectives/Hypothesis: Tumor burden has been confirmed as one of the important indicators in disease control after treatment for various types of malignancies. This report aims to document the value of the primary tumor volume of nasopharyngeal carcinoma [gross tumor volume of the primary site (GTV‐P)] in predicting the treatment outcome after high‐dose definitive radiation therapy.

Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1α/miR-210/Bcl-2 pathway in colon cancer cells

Autophagy is an evolutionarily conserved cellular response to conditions of stress such as hypoxia, which induce radioresistance in cancer cells. We studied the mechanism of action of hypoxia on autophagy and radiosensitivity in colon cancer cells. In the human colon cancer cell lines SW480 and SW620, autophagosomes were analyzed to evaluate autophagy by flow cytometry. The expression of hypoxia inducible factor-1α (HIF-1α), Bcl-2, and miR-210 was detected by western blotting and quantitative real-time polymerase chain reaction (PCR). HIF-1α and miR-210 inhibition was induced by siRNA transfections. Apoptosis detection and colony assays were performed to determine radiosensitivity. HIF-1α and miR-210 showed a significant increase under hypoxic condition. The inhibition of HIF-1α decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. Under hypoxia, HIF-1α induces miRNA-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. Our results imply that autophagy contributes to the reduction of radiosensitivity in hypoxic environment, and the process is mediated through the HIF-1α/miR-210/Bcl-2 pathway in human colon cancer cells.

Consensus recommendations for management of head and neck cancer in Asian countries: A review of international guidelines

Head and neck cancer (HNC) is a disease of the upper aerodigestive tract and is one of the most frequently diagnosed cancers worldwide. A high rate of cancers involving the head and neck are reported across the Asian region, with notable variations between countries. Disease prognosis is largely dependent on tumor stage and site. Patients with early stage disease have a 60-95% chance of cure with local therapy. Early diagnosis and appropriate treatment are important to increase the likelihood of cure and survival. However, the majority of patients present with locally advanced disease and require multimodality treatment. This necessitates, a multidisciplinary approach which is essential to make appropriate treatment decisions, particularly with regards to tolerability, costs, available infrastructure and quality of life issues. Unfortunately, majority of the studies that dictate current practice have been developed in the west where diseases biology, patient population and available infrastructure are very different from those in the Asian continent. With this in mind an expert panel of Head and Neck Oncologists was convened in May 2012 to review the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) clinical practice guidelines and develop practical recommendations on the applicability of these guidelines on the management of head and neck cancer for Asian patients. The objective of this review and consensus meeting was to suggest revisions, to account for potential differences in demographics and resources, to the NCCN and ESMO guidelines, to better reflect current clinical management of head and neck cancer within the Asian region for health care providers. These recommendations, which reflect best clinical practice within Asia, are expected to benefit practitioners when making decisions regarding optimal treatment strategies for their patients.

Pretreatment (18)F-FDG uptake heterogeneity can predict survival in patients with locally advanced nasopharyngeal carcinoma--a retrospective study.

BackgroundIntratumoural heterogeneity has been demonstrated to be a strong indicator of malignant transformation. Our study was to investigate pretreatment 18 F-FDG parameters, including 18 F-FDG based heterogeneity for predicting survival in patients with locally advanced nasopharyngeal carcinoma (NPC).MethodsForty newly diagnosed, biopsy-proven locally advanced NPC patients who underwent 18 F-FDG PET/CT were retrospectively included. The following PET parameters were assessed: maximum and mean standardised uptake value (SUVmax and SUVmean), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and intratumoral heterogeneity index (HI). The previous parameters were recorded both for the primary tumor (-T) and neck lymph nodes (-N). The following endpoints were evaluated: local control (LC), progression-free survival (PFS) and overall survival (OS). The survival analyses were performed using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test.ResultsPatients with a lower HI-T, SUVmax-T, SUVmean-T and TLG-T had significantly better 2-year LC. In predicting PFS, we found that both lower HI-T and HI-N had significantly better prognosis. However, the OS was only statistically associated with HI-T.Conclusion18 F-FDG based heterogeneity appears to be an potential predicator of patient survival after treatment.

Effect of dosimetric factors on occurrence and volume of temporal lobe necrosis following intensity modulated radiation therapy for nasopharyngeal carcinoma: A case-control study

PURPOSE To determine dosimetric risk factors for the occurrence of temporal lobe necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT) and to investigate the impact of dose-volume histogram (DVH) parameters on the volume of TLN lesions (V-N). METHODS AND MATERIALS Forty-three NPC patients who had developed TLN following IMRT and 43 control subjects free of TLN were retrospectively assessed. DVH parameters included maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean), absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), and doses covering certain volumes (Dvs) from 0.25 to 6.0 cm(3) (D0.25-D6.0). V-Ns were quantified with axial magnetic resonance images. RESULTS DVH parameters were ubiquitously higher in temporal lobes with necrosis than in healthy temporal lobes. Increased Vds and Dvs were significantly associated with higher risk of TLN occurrence (P<.05). In particular, Vds at a dose of ≥70 Gy were found with the highest odds ratios. A common increasing trend was detected between V-N and DVH parameters through trend tests (P for trend of <.05). Linear regression analysis showed that V45 had the strongest predictive power for V-N (adjusted R(2) = 0.305, P<.0001). V45 of <15.1 cm(3) was relatively safe as the dose constraint for preventing large TLN lesions with V-N of >5 cm(3). CONCLUSIONS Dosimetric parameters are significantly associated with TLN occurrence and the extent of temporal lobe injury. To better manage TLN, it would be important to avoid both focal high dose and moderate dose delivered to a large area in TLs.

Association between Systemic Chemotherapy before Chemoradiation and Increased Risk of Treatment-Related Pneumonitis in Esophageal Cancer Patients Treated with Definitive Chemoradiotherapy

Background: There is limited information on risk factors for treatment-related pneumonitis in esophageal cancer patients. Aim of the Study: To determine factors associated with treatment-related pneumonitis in esophageal cancer patients treated with definitive chemoradiotherapy. Materials and Methods: We retrospectively reviewed clinical data from esophageal cancer patients treated with definitive chemoradiotherapy from 2000 to 2003. Demographic, clinical, and treatment-related data were collected for all patients. The time to occurrence of grade ≥2 pneumonitis was calculated from the end of radiotherapy. Univariate analyses were performed to determine the existence of any association between patient demographic, clinical, or treatment characteristics and pneumonitis. Results: In total, 96 patients were included in the study with a median follow-up of 8 months (range, <1–48 months). Among them, 23 patients also received an average of two cycles of systemic chemotherapy before the initiation of concurrent chemoradiation. The incidence of grade ≥2 pneumonitis was 22% at 1 year. Systemic chemotherapy before concurrent chemoradiation was significantly associated with an increased risk of grade ≥2 pneumonitis (p = 0.003), with the 1-year incidence of grade ≥2 pneumonitis for patients with and without systemic chemotherapy being 49 and 14%, respectively. No other clinical or dosimetric factors investigated were associated with the risk of grade ≥2 pneumonitis. Conclusions: Systemic chemotherapy before concurrent chemoradiation was significantly associated with an increased risk of grade ≥2 pneumonitis, suggesting that induction chemotherapy may have sensitized the lung tissue to radiation damage in esophageal cancer patients.