The Inflammatory Cytokine Profile of Patients with Malignant Pleural Effusion Treated with Pleurodesis.

Patients with malignant pleural effusion (MPE) who underwent successful pleurodesis survive longer than those for whom it fails. We hypothesize that the therapy-induced inflammatory responses inhibit the cancer progression, and thereby lead to a longer survival. Thirty-three consecutive patients with MPE that were eligible for bleomycin pleurodesis between September 2015 and December 2017 were recruited prospectively. Nineteen patients (57.6%) achieved fully or partially successful pleurodesis, while 14 patients either failed or survived less than 30 days after pleurodesis. Two patients without successful pleurodesis were excluded because of missing data. Interleukin (IL)-1 beta, IL-6, IL-10, transforming growth factor beta, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor in the pleural fluid were measured before, and after 3 and 24 h of pleurodesis. Their pleurodesis outcome and survival were monitored and analyzed. Patients who underwent successful pleurodesis had a longer survival rate. Patients without successful pleurodesis had significantly higher TNF-α and IL-10 levels in their pleural fluid than in the successful patients before pleurodesis. Following pleurodesis, there was a significant increment of IL-10 in the first three hours in the successful patients. In contrast, significant increments of TNF-α and IL-10 were found in the unsuccessful patients between 3 and 24 h after pleurodesis. The ability to produce specific cytokines in the pleural space following pleurodesis may be decisive for the patient's outcome and survival. Serial measurement of cytokines can help allocate the patients to adequate treatment strategies. Further study of the underlying mechanism may shed light on cytokine therapies as novel approaches.

Clinical outcomes of chemical pleurodesis using a minocycline.

BACKGROUND: Pleurodesis is often used to prevent the re-accumulation of a malignant pleural effusion (MPE). Intrapleural urokinase (IPUK) therapy facilitates lung re-expansion for patients with loculated MPE or a trapped lung that allows subsequent pleurodesis. MPE management has been traditionally regarded as a symptomatic treatment. We tried to evaluate their impact on patient survival. METHODS: There were 314 consecutive patients with symptomatic MPE that underwent minocycline pleurodesis with ( n = 109) and without ( n = 205) the antecedent IPUK therapy between September 2005 and August 2015, who were recruited for the pleurodesis outcome and survival analysis. RESULTS: The rate of successful pleurodesis was similar between the simple pleurodesis group and the IPUK therapy group followed by the pleurodesis group (69.0% versus 70.5%; p = 0.804). The patients who succeeded pleurodesis had a longer survival rate than those who failed in either the simple pleurodesis group (median, 414 versus 100 days; p < 0.001) or the IPUK therapy followed by pleurodesis group (259 versus 102 days; p < 0.001). The survival differences remained when the lung and breast cancer patients were studied separately. CONCLUSION: Successful pleurodesis translated into a better survival rate that promotes performing pleurodesis on lung re-expansion. The apparent shorter survival of the patients with loculated MPE or trapped lung, and those that did not respond to the IPUK therapy, lowered the probability of the survival benefit through the simple physical barrier by the fibrin formation to prevent the tumor spreading. The successfully induced inflammatory response by minocycline is supposed to prohibit the tumor invasion and metastasis. Further studies are warranted to clarify the mechanism and provide opportunities to develop novel therapeutic strategies.

Conventional transbronchial needle aspiration is promising for identifying EGFR mutations in lung adenocarcinoma.

BACKGROUND: Conventional transbronchial needle aspiration (TBNA) is advantageous for the one-step diagnosis and staging of lung adenocarcinoma under topical anesthesia and conscious sedation. We examined its efficacy for identifying EGFR mutations. METHODS: Forty-seven patients with proven or suspected lung adenocarcinoma indicated for hilar-mediastinal lymph node (LN) staging between June 2011 and December 2017 were enrolled. The cellblock was prepared using the plasma-thrombin method. TaqMan PCR was used to detect mutations. Considering cost effectiveness, only the sample with the highest tumor cell fraction in the same patient was chosen for analysis. RESULTS: TBNA provided positive results of malignancy in 27 patients. Seventeen patients (63.0%) had cellblocks eligible for mutation testing. Bronchial biopsy (n = 6), neck LN fine needle aspiration (n = 1), and brushing (n = 1), provided higher tumor cell fractions for analysis in eight patients. TBNA was the exclusive method used in nine patients (19.1%). For patients with an inadequate TBNA cellblock, bronchial biopsy (n = 5), neck LN fine needle aspiration (n = 3), computed tomography-guided transthoracic needle biopsy (n = 1), and brushing (n = 1) were used for analysis. Modification to specimen processing to prevent exhaustion by cytology after June 2016 improved the adequacy of cellblock samples (9/10, 90% vs. 8/17, 47.1%; P = 0.042). CONCLUSIONS: These findings suggest the promising role of conventional TBNA and highlight the challenges of doing more with less in an era of precision medicine.

G-Protein Coupled Estrogen Receptor in Breast Cancer.

The G-protein coupled estrogen receptor (GPER), an alternate estrogen receptor (ER) with a structure distinct from the two canonical ERs, being ERα, and ERß, is expressed in 50% to 60% of breast cancer tissues and has been presumed to be associated with the development of tamoxifen resistance in ERα positive breast cancer. On the other hand, triple-negative breast cancer (TNBC) constitutes 15% to 20% of breast cancers and frequently displays a more aggressive behavior. GPER is prevalent and involved in TNBC and can be a therapeutic target. However, contradictory results exist regarding the function of GPER in breast cancer, proliferative or pro-apoptotic. A better understanding of the GPER, its role in breast cancer, and the interactions with the ER and epidermal growth factor receptor will be beneficial for the disease management and prevention in the future.

Estrogen, Estrogen Receptor and Lung Cancer.

Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER) in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR), and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

Pleural fluid osteopontin, vascular endothelial growth factor, and urokinase-type plasminogen activator levels as predictors of pleurodesis outcome and prognosticators in patients with malignant pleural effusion: a prospective cohort study.

BACKGROUND: Rapidly growing cancer cells secrete growth-promoting polypeptides and have increased proteolytic activity, contributing to tumor progression and metastasis. Their presentation in malignant pleural effusion (MPE) and their predictive value for the outcome of pleurodesis and survival were studied. METHODS: Between February 2011 and March 2012, MPE samples were prospectively collected from 61 patients. Twenty-five patients with non-malignant pleural effusion in the same period were included as controls. Pleural fluid osteopontin (OPN), vascular endothelial growth factor (VEGF), and urokinase-type plasminogen activator (uPA) concentrations were measured. RESULTS: Patients with MPE had higher pleural fluid OPN, VEGF, and uPA concentrations than those with non-malignant pleural effusion, but only differences in VEGF were statistically significant (p = 0.045). Patients with distant metastases had significantly elevated pleural fluid VEGF concentrations than those without (p = 0.004). Pleural fluid OPN, VEGF, and uPA concentrations were positively correlated in most patients. However, there was no significant difference in pleural fluid OPN, VEGF, and uPA concentrations between patients with successful pleurodesis and those without. There was also no significant difference in cancer-specific survival between sub-groups with higher and lower pleural fluid OPN, VEGF, or uPA concentrations. Patients with successful pleurodesis had significantly longer cancer-specific survival than those without (p = 0.015). CONCLUSIONS: Pleural fluid OPN, VEGF, and uPA concentrations are elevated in MPE but are not satisfactory predictors of pleurodesis outcome or survival. Patients with higher pleural fluid VEGF concentration have higher risk of distant metastasis. Evaluating the benefits of therapy targeting the VEGF pathway in these patients warrants further studies.

Comparison of 19-gauge eXcelon and WANG MW-319 transbronchial aspiration needles.

Conventional transbronchial needle aspiration (TBNA) using 19-gauge needles can obtain larger histological specimens for hilar-mediastinal diagnosis. A new 19-gauge eXcelon needle was introduced in Taiwan in July 2012. We prospectively enrolled patients with hilar-mediastinal lesions and pathology results of suspected benign origin or lymphoproliferative processes, to perform TBNA using a 19-gauge eXcelon needle, between July 2012 and December 2012. The results were compared with historical control of TBNA using a WANG MW-319 needle between January 2011 and June 2012. The procedure was performed by the same pulmonologist, and rapid on-site cytologic evaluation was used. The 19-gauge eXcelon needle was used in nine patients with 15 lymph nodes aspirated, with a mean diameter of 23.3 ± 10.7 mm. The mean number of needle passes was 2.7 ± 1.4, with a diagnostic accuracy of 77.8%. The MW-319 needle was used in 12 patients with 18 lymph nodes aspirated, with a mean diameter of 21.3 ± 5.7 mm. The mean number of needle passes was 2.2 ± 0.4, with a diagnostic accuracy of 75.0%. Neither technical nor major clinical complications were noted in either group. We concluded that the 19-gauge eXcelon needle was as safe and effective as the MW-319 needle. A more adequate specimen could be obtained and fewer needle passes were required with the MW-319 needle, although the difference did not reach significance.

Second primary lung cancers among breast cancer patients treated with anti-estrogens have a longer cancer-specific survival.

BACKGROUND/AIM: Estrogen is thought to play an important role in lung cancer carcinogenesis and progression. The incidence and survival of second primary lung cancer among breast cancer patients with and without anti-estrogen therapy were evaluated. PATIENTS AND METHODS: All women diagnosed with breast cancer and treated at the Sun Yat-Sen Cancer Center between January 2000 and December 2009 were included and followed-up for occurrence and/or death from lung cancer until December 2011. RESULTS: Twenty-six women developed second primary lung cancer among 6,361 breast cancer patients. All but one were adenocarcinoma and none had a smoking habit. Seventeen (65.4%) patients had previously received anti-estrogen treatment. The relative risk of developing second primary lung cancer among those who have received anti-estrogens for breast cancer and those who have not was 1.01 (95% confidence interval (CI)=0.45~2.28; p=0.970). Second primary lung cancer patients who have received anti-estrogens had a longer cancer-specific survival (p=0.007). The multivariate Cox proportional hazards analysis showed that anti-estrogen therapy remained an independent prognostic factor with a hazard ratio of 0.11 (95% CI=0.01~0.97, p=0.002) for second primary lung cancer patients. CONCLUSION: The results of this study further support the fact that estrogen adversely affects the prognosis of patients with lung cancer. However, the role of estrogen in lung cancer carcinogenesis remains to be determined.

Estrogen adversely affects the prognosis of patients with lung adenocarcinoma.

Estrogen has been postulated to contribute to the development and progression of lung cancer. We examined the epidemiologic evidence, explored the characteristics of estrogen receptors (ER) in lung adenocarcinoma, and investigated the effect of estrogen on lung cancer cell migration, including the signaling pathway involved. For epidemiologic evidence, a total of 1434 consecutive non-small cell lung cancer patients who underwent standardized staging and homogenous treatment were prospectively enrolled from January 2002 to December 2008, and followed until December 2012. The possible prognostic factors to be analyzed included stage, age, gender, menopausal status, smoking history and histology. For laboratory study, lung cancer cell lines A549 and PE089 and malignant pleural effusions from the patients with lung adenocarcinoma were used. We found that the premenopausal patients had more advanced disease and a shorter survival among the never-smoking female patients with lung adenocarcinoma. ERß was the predominant ER in the lung cancer cell lines. We proposed a different pathway that estrogen upregulated the expression of osteopontin and then promoted cell migration through αvß3 integrin binding and activated MEK-ERK signaling pathway, which is a common downstream pathway with epidermal growth factor receptor (EGFR) activation. An additive effect of ER antagonists and EGFR antagonists on the inhibition of cell migration was also noted. Our results suggest that estrogen adversely affects the prognosis of patients with lung adenocarcinoma. Osteopontin contributed to the cross-talk between ER and EGFR signaling pathways. Estrogen, with its receptor, has the potential to be a prognosticator and a therapeutic target in lung cancer.

Multimodality treatment and long-term follow-up of the primary pulmonary lymphoepithelioma-like carcinoma.

INTRODUCTION: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a very rare subtype of non-small-cell lung cancer. Most cases are reported in Southeast Asia and are associated with Epstein-Barr virus infections. Because of its rare incidence, the optimal treatment and the results of long-term follow-up are not well understood. This study is an attempt to discover the multimodality treatment results of the primary pulmonary LELC. METHODS: This retrospective study enrolled 21 patients with primary pulmonary LELC treated at 2 hospitals with a multimodality approach, including surgery, chemotherapy, radiotherapy, and targeted therapy. RESULTS: The median follow-up time is 5.9 years and the median survival is 6.4 years. The median overall survival for patients with stage III and with stage IV disease is 3.4 years. In early-stage primary pulmonary LELC, surgery and adjuvant chemotherapy provided good treatment outcome. Advanced primary pulmonary LELC is relatively more chemosensitive and radiosensitive. CONCLUSION: Patients with primary pulmonary LELC showed better prognosis than those with other types of non-small-cell lung cancer and achieved longer survival under multimodality treatment. This disease character is similar to that of nasopharyngeal carcinoma. Accurate pathologic diagnosis is recommended before the treatment. For advanced diseases, platinum-based doublet chemotherapy can be considered the first-line treatment. Radiation dose should consider tumor location, and 5000 to 7000 cGy is frequently applied for pulmonary LELC.

Sex-associated differences in non-small cell lung cancer in the new era: is gender an independent prognostic factor?

BACKGROUND: Women with non-small cell lung cancer (NSCLC) appear to have better survival. This study aimed to evaluate sex differences in NSCLC in recent years. The true effect of gender on the overall survival was analyzed taking other prognostic factors into account. METHODS: A cohort of consecutive NSCLC patients was prospectively enrolled from January 2002 to December 2005, and followed-up until December 2006. They were clinically and pathologically staged and underwent homogenous treatment algorithms. Demographics, histology, and disease stage between sexes were compared. The clinical prognostic factors to be analyzed in addition to gender included stage, age, smoking history and histology. The overall survival of females and males within relevant subgroups defined by smoking history and histology was also compared. RESULTS: Of the 738 patients, 695 were analyzed with a definite stage (94.2%; 315 females and 380 males), which was similar in both sexes. Females were younger (median age: 59.5 years vs. 65.0 years; P<0.001) and more likely to have adenocarcinoma (81% vs. 60.5%; P<0.001). Patients with earlier stage, younger patients, never-smokers and females had better overall survival in univariate analyses and no significant survival difference was noted between adenocarcinoma and squamous cell carcinoma. Multivariate analyses demonstrated age, smoking history and gender to have a hazard ratio 1.46 (95% confidence interval, CI 1.21-1.76; P<0.001), 1.27 (95% CI 0.97-1.65; P=0.082), and 1.18 (95% CI 0.90-1.55; P=0.226), respectively. Subgroup analyses revealed the survival of never-smoker males with adenocarcinoma was similar to that of females. CONCLUSIONS: There are sex-related differences in the clinico-pathologic characteristics and survival of NSCLC patients. The survival advantages of females could be attributed to the younger age and lower smoking prevalence. Never-smokers with adenocarcinoma should be given special attention regardless of sex as they imply better survival with different treatment outcomes.

High efficacy of erlotinib in Taiwanese NSCLC patients in an expanded access program study previously treated with chemotherapy.

PURPOSE: Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which has demonstrated a survival benefit in non-small-cell lung cancer (NSCLC) patients. An open label phase II study was conducted in Taiwanese patients with NSCLC to evaluate its efficacy. METHODS: Patients with proven stage IIIB/IV NSCLC who had received at least one line of standard chemotherapy or radiotherapy were enrolled into this study. All patients were given oral erlotinib, 150mg/day till disease progression. RESULTS: From May 2005 to July 2006, 300 patients were entered from 14 hospitals in Taiwan. This analysis was based on 299 patients who received at least one dose of erlotinib. The best response rates were a 29% partial response and 44% stable disease in 273 patients who had response data available. Non-smoking (p=0.033), adenocarcinoma/BAC (p=0.0027), female (p=0.0013), aged less than 65 years (p=0.0115), stage IV (p=0.0492), patients with skin rash (p=0.0216), and a higher grade of skin rash (p=0.003) were significantly correlated with response to treatment. Skin rash was a common adverse event (any grade: 84%, Gr 3-4: 16%). The median time to disease progression was 5.6 months. Cox regression model for progression free survival showed patients most at risk of early progression were males of low performance status having squamous cell carcinoma. CONCLUSIONS: This was the largest multicenter prospective clinical study of NSCLC in Taiwan. The results demonstrated the excellent response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese NSCLC patients who had been previously treated with chemotherapy or radiotherapy.

Transbronchial needle aspiration accurately diagnoses subcentimetre mediastinal and hilar lymph nodes detected by integrated positron emission tomography and computed tomography.

OBJECTIVE AND BACKGROUND: Integrated PET and CT (PET/CT) is accurate in detecting hilar-mediastinal metastases. However, it has a moderate positive predictive value, necessitating pathological verification, especially in situations in which the result would make a difference to treatment. This study aimed to evaluate the performance of transbronchial needle aspiration (TBNA) for hilar-mediastinal lesions suspicious on PET/CT. METHODOLOGY: A retrospective study was conducted on 19 patients with a total of 25 positive hilar-mediastinal lymph nodes localized on PET/CT. Standard TBNA technique with rapid on-site cytopathology was performed. RESULTS: The mean short-axis diameter of the positive lymph nodes identified on PET/CT was 9.9 +/- 3.0 mm. The sensitivity, specificity and diagnostic accuracy of PET/CT-guided TBNA were 81.8%, 100% and 84%, respectively. The number of needle passes to successful lymph node aspiration or a diagnosis of cancer was 2.36 +/- 0.49. Nine of the 25 positive lymph nodes (36%) on PET/CT were smaller than 1.0 cm. The accuracy and sensitivity of TBNA for these subcentimetre nodes was 88.9% and 87.5%, respectively. TBNA replaced surgical sampling in 15 patients (78.9%) with positive lymph nodes on PET/CT. In seven non-small cell lung cancer patients, diagnosis and staging were possible in the one procedure. No complications were encountered. CONCLUSION: PET/CT can identify small malignant lymph nodes that can then be successfully biopsied by TBNA with on-site cytopathology.

Computed tomography characteristics of primary pulmonary lymphoepithelioma-like carcinoma.

Primary pulmonary lymphoepithelioma-like carcinoma is a very rare subtype of lung cancer. This report documents the CT features of 16 Chinese patients diagnosed with primary pulmonary lymphoepithelioma-like carcinoma from January 1999 to December 2005. A pre-treatment CT was used to assess the tumour site, size, borders, pleural and vascular involvement, and the presence of lymph node involvement. The majority of the patients were female non-smokers with centrally located tumours. Lymph node involvement and bronchial and vascular encasement were frequent. In an Epstein-Barr virus endemic area, primary pulmonary lymphoepithelioma-like carcinoma is an important differential diagnosis to consider.

A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy.

PURPOSE: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. METHODS AND MATERIALS: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. RESULTS: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. CONCLUSION: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

Incidence of chemotherapy-induced nausea and vomiting in Taiwan: physicians' and nurses' estimation vs. patients' reported outcomes.

BACKGROUND: The major objective of the study was to determine the incidence and prevalence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) among patients receiving chemotherapy and assess the accuracy with which medical providers perceive the incidence of CINV in their practice. METHODS: Specialists, residents and nurses (medical providers) from two cancer centers in Taiwan estimated the incidence of acute and delayed CINV. Chemotherapy-naive patients from the same centers then completed a 5-day nausea and vomiting diary following highly and moderately emetogenic chemotherapy (HEC and MEC) to determine the actual incidence of acute and delayed CINV. Daily nausea ratings were recorded on a 100-mm visual analogue scale (VAS). No nausea was defined as a nausea VAS score <5 mm. Vomiting episodes were also recorded. Nausea and vomiting were defined as acute and delayed based on whether they occurred during the first 24 h after chemotherapy, or during days 2-5 after chemotherapy, respectively. RESULTS: In the two oncology centers, 37 medical providers (13 specialists, 4 residents, 20 nurses) and 107 patients were enrolled. The mean patient age was 49.2 years with 76% female and 74% having breast cancer. Of the 107 patients, 39% received HEC and 61% received MEC, and 77% received a 5-HT3 receptor antagonist and 94% received dexamethasone. There were no significant differences between patients with acute CINV and delayed CINV in terms of demographics, chemotherapy treatment or antiemetic treatment. The proportion of patients without alcohol use was significantly higher among patients with delayed CINV than among those with non-delayed CINV. Good control of CINV during the acute period correlated with the control of delayed emesis. There were no significant differences between specialists', residents', and nurses' estimations of the incidence rates of CINV. For HEC given to chemotherapy-naïve patients, the medical providers estimated acute CINV to be 44/41% and delayed CINV to be 61/53%, respectively. However, patient diaries revealed acute CINV to be 43/21% and delayed CINV to be 64/60%, respectively. For MEC given to chemotherapy-naive patients, medical providers estimated acute CINV to be 39/36% and delayed CINV to be 44/39%, respectively. However, patient diaries revealed acute CINV to be 55/18% and delayed CINV to be 74/55%, respectively. CONCLUSIONS: Medical providers significantly overestimated the incidence of acute vomiting by 20% and 18% in HEC and MEC patients, respectively. While they correctly estimated the rate of delayed vomiting in HEC patients, they underestimated it by 16% in MEC patients. With respect to nausea, medical providers correctly estimated rates of both acute and delayed nausea in HEC patients, but significantly underestimated rates of acute and delayed nausea by 16% and 30%, respectively, in MEC patients.

Prognostic significance of parapharyngeal space venous plexus and marrow involvement: potential landmarks of dissemination for stage I-III nasopharyngeal carcinoma.

PURPOSE: To determine whether the parapharyngeal space venous plexus and marrow of the skull base bones are anatomic landmarks of the potential routes for the spread of disease for Stage I-III (American Joint Commission on Cancer 1997 staging system) nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 364 patients with NPC were enrolled in this study. The selection criteria were Stage I-III disease and primary radiotherapy at our hospital between 1990 and 2001. All patients had undergone MRI to evaluate the head-and-neck tumors. Patients who had undergone inadequate radiotherapy at a dose of <60 Gy and/or preradiotherapy chemotherapy before the imaging evaluation were excluded from the study. RESULTS: Of the 364 patients treated between 1990 and 2001, 163 (44.8%) had low-risk Stage I-III NPC (without parapharyngeal space extension or T3 disease). The 5-year distant metastasis-free survival rate, with and without adjuvant chemotherapy, was 97% and 96%, respectively. The remaining 201 patients had Stage II-III with parapharyngeal space extension or T3 disease. Their 5-year recurrence-free survival rate, with and without adjuvant chemotherapy, was 76.8% and 53.2% (p = 0.01), respectively. CONCLUSION: Our findings suggest that the risk of distant metastasis in Stage I-III NPC patients without parapharyngeal space extension or T3 disease is extremely low. Invasion into the parapharyngeal space venous plexus and marrow of the skull base bones is associated with distant metastasis, and involvement of these anatomic sites is considered a potential route for hematogenous disease spread in patients with Stage I-III NPC.

Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionated radiotherapy and concomitant chemotherapy.

PURPOSE: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions. PATIENTS AND METHODS: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday-Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation. RESULTS: With a median follow-up of 57 months (range: 28-94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks. CONCLUSION: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.