Jianji Pan

NASOPHARYNGEAL CARCINOMA TREATED WITH REDUCED-VOLUME INTENSITY-MODULATED RADIATION THERAPY: REPORT ON THE 3-YEAR OUTCOME OF A PROSPECTIVE SERIES

PURPOSEnTo evaluate the efficacy of intensity-modulated radiotherapy (IMRT) using reduced clinical target volumes (CTV) in the treatment of nasopharyngeal carcinoma (NPC).nnnMETHODS AND MATERIALSnBetween August 2003 and December 2006, 323 patients with NPC were treated with IMRT according to this institutional protocol. Presenting stages were Stage II in 63, Stage III in 166, and Stage IVA/B in 94 patients. High-risk CTV encompassed gross tumor volume and entire nasopharyngeal mucosa with a margin. A reduced CTV was delineated for the remaining subclinical regions adjacent to the primary disease. Uninvolved neck nodes were delineated according to the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) consensus excluding the deep jugular (i.e., lymph nodes in retrostyloid space above C1 vertebra) and submental nodes. Patients with locoregionally advanced diseases also received cisplatin-based chemotherapy.nnnRESULTSnWith a median follow-up of 30 months (range, 4-53 months), 12, 6, and 26 patients had developed local, regional, and distant failures, respectively. The 3-year estimated local control, regional control, metastasis-free survival, disease-free survival and overall survival were 95%, 98%, 90%, 85%, and 90%, respectively. Multivariate analyses revealed that T-classification had no predictive value for outcome, whereas N-classification was significant for predicting metastasis-free (p = 0.005) and overall survival (p =0.006). Ten patients (7.8%) experienced Grade II xerostomia at 24 months after treatment. No Grade III or IV late-toxicities were observed. Two patients died of treatment-induced complications.nnnCONCLUSIONnThe IMRT approach using a reduced target volume provided favorable outcome for NPC with acceptable toxicity. This strategy needs to be optimized and then tested in a prospective setting to learn whether further improvement can be achieved.

Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: Experience of 370 consecutive cases

IntroductionTo investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) after induction chemotherapy, with or without concomitant chemotherapy.MethodsBetween August 2003 and March 2007, 370 patients with locoregionally advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62, stage III in 197, and stage IVA/B in 111 patients. All patients except for 36 patients with cervical lymphadenopathy of 4 cm or less in diameter received 2 cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received cisplatin-based concurrent chemotherapy as well.ResultsWith a median follow-up time of 31 months (range 5 to 61 months), the 3-year local control, regional control, metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate analyses revealed that both age (≤ 60 vs. >60) and N-classification are significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95% confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95% confidence interval [CI] 1.235-5.533); And N-classification is the only significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279-3.098). T-classification and concurrent chemotherapy were not significant prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis revealed that concurrent chemotherapy provided no significant benefit to IMRT in locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4 acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity including xerostomia was observed. However, two patients treated with IMRT and neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment related complications.ConclusionIMRT following neoadjuvant chemotherapy produced a superb outcome in terms of local control, regional control, MFS, DFS, and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy is urgently needed for distant control in patients diagnosed with locoregionally advanced NPC.

Intensity-modulated radiation therapy in the salvage of locally recurrent nasopharyngeal carcinoma.

PURPOSEnLocal recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC.nnnMETHODS AND MATERIALSnBetween August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy.nnnRESULTSnThe median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors.nnnCONCLUSIONnReirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

Number and location of positive nodes, postoperative radiotherapy, and survival after esophagectomy with three-field lymph node dissection for thoracic esophageal squamous cell carcinoma

PURPOSEnTo analyze influences of the number and location of positive lymph nodes and postoperative radiotherapy on survival for patients with thoracic esophageal squamous cell carcinoma (TE-SCC) treated with radical esophagectomy with three-field lymphadenectomy.nnnMETHODS AND MATERIALSnA total of 945 patients underwent radical esophagectomy plus three-field lymph node dissection for node-positive TE-SCC at Fujian Provincial Tumor Hospital between January 1993 and March 2007. Five hundred ninety patients received surgery only (S group), and 355 patients received surgery, followed 3 to 4 weeks later by postoperative radiotherapy (S+R group) to a median total dose of 50 Gy in 25 fractions. We assessed potential associations among patient-, tumor-, and treatment-related factors and overall survival.nnnRESULTSnFive-year overall survival rates were 32.8% for the entire group, 29.6% for the S group, and 38.0% for the S+R group (p = 0.001 for S vs. S+R). Treatment with postoperative radiotherapy was particularly beneficial for patients with ≥3 positive nodes and for those with metastasis in the upper (supraclavicular and upper mediastinal) region or both the upper and lower (mediastinal and abdominal) regions (p < 0.05). Postoperative radiotherapy was also associated with lower recurrence rates in the supraclavicular and upper and middle mediastinal regions (p < 0.05). Sex, primary tumor length, number of positive nodes, pathological T category, and postoperative radiotherapy were all independent predictors of survival.nnnCONCLUSIONSnPostoperative radiotherapy was associated with better survival for patients with node-positive TE-SCC, particularly those with three or more positive nodes and positive nodes in the supraclavicular and superior mediastinal regions.

Postoperative radiation therapy with or without concurrent chemotherapy for node-positive thoracic esophageal squamous cell carcinoma

PURPOSEnTo retrospectively compare the efficacy of radiation therapy (RT) and chemotherapy plus RT (CRT) for the postoperative treatment of node-positive thoracic esophageal squamous cell carcinoma (TESCC) and to determine the incidence and severity of toxic reactions.nnnMETHODS AND MATERIALSnWe retrospectively reviewed data from 304 patients who had undergone esophagectomy with 3-field lymph node dissection for TESCC and were determined by postoperative pathology to have lymph node metastasis without distant hematogenous metastasis. Of these patients, 164 underwent postoperative chemotherapy (cisplatin 80 mg/m(2), average days 1-3, plus paclitaxel 135 mg/m(2), day 1; 21-day cycle) plus RT (50 Gy), and 140 underwent postoperative RT alone.nnnRESULTSnThe 5-year overall survival rates for the CRT and RT groups were 47.4% and 38.6%, respectively (P=.030). The distant metastasis rate, the mixed (regional lymph node and distant) metastasis rate, and the overall recurrence rate were significantly lower in the CRT group than in the RT group (P<.05). However, mild and severe early toxic reactions, including neutropenia, radiation esophagitis, and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P<.05). No significant differences in incidence of late toxic reactions were found between the 2 groups.nnnCONCLUSIONSnOur results show that in node-positive TESCC patients, postoperative CRT is significantly more effective than RT alone at increasing the overall survival and decreasing the rates of distant metastasis, mixed metastasis, and overall recurrence. Severe early toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.

Cervical lymph node metastasis classified as regional nodal staging in thoracic esophageal squamous cell carcinoma after radical esophagectomy and three-field lymph node dissection

BackgroundLymph node metastasis (LNM) is most common in esophageal squamous cell carcinoma (SCC). The bi-directional spread is a key feature of LNM in patients with thoracic esophageal SCC (TE-SCC). The purpose of this study was to analyze the prognostic factors of survival in patients with TE-SCC with cervical lymph node metastasis (CLM) and validate the staging system of the current American Joint Committee on Cancer (AJCC) in a cohort of Chinese patients.MethodsOf 1715 patients with TE-SCC who underwent radical esophagectomy plus three-field lymph node dissection at a single hospital between January 1993 and March 2007, 547 patients who had pathologically confirmed CLM (296 had surgery only and 251 had surgeryu2009+u2009postoperative radiotherapy) were included in this study. The locations of the lymph nodes (LNs) were classified based on the guidelines of the Japanese Society for Esophageal Diseases.ResultsThe rate of CLM was 31.9% for all patients and was 44.2%, 31.5%, and 14.4% for patients with upper, middle, and lower TE-SCC, respectively (Pu2009<u20090.0001). The rates of metastasis to 101 (paraesophageal lymph nodes), 104 (supraclavicular lymph nodes), 102 (deep cervical lymph nodes) and 103 (retropharyngeal lymph nodes) areas were 89.0%, 25.6%, 3.7% and 0.5%, respectively. The 5-year overall survival (OS) rate with CLM was 27.7% (median survival, 27.5xa0months). The 5-year OS rates were 21.3% versus 34.2% (median survival, 21.9xa0months versus 35.4xa0months) for after surgery only versus surgeryu2009+u2009postoperative radiotherapy, respectively (Pu2009<u20090.0001 for both). Multivariate analysis showed that the independent prognostic factors for survival were sex, pT stage, pN stage, number of fields with positive LNs, and treatment modality. In surgery only group, the 5-year OS rates were 24.1%, 16.2% and 11.7%, respectively, when there was metastasis to 101 LN alone, 104 LN alone or both 101 LN and 104 LN. The 5-year OS rates were 17.7%, 22.5% and 31.7%, for patients with upper, middle and lower TE-SCC , respectively (Pu2009=u20090.112). The 5-year OS rates were 43.0%, 25.5%, 10.2% in patients with 1 field (cervical LNs), 2 fields (cervicalu2009+u2009mediastinal, and/or cervicalu2009+u2009abdominal LNs), and 3 fields (cervicalu2009+u2009mediastinalu2009+u2009abdominal LNs) positive LNs, respectively (Pu2009<u20090.0001). The number of fields of positive LNs did not impact the OS according to different pN stage (all Pu2009>u20090.05).ConclusionPatients with TE-SCC with CLM have better prognosis, which supports the current AJCC staging system for esophageal SCC.

Prognostic factors in patients with thoracic esophageal carcinoma staged pT 1-4a N 0 M 0 undergone esophagectomy with three-field lymphadenectomy

BACKGROUNDnTo analyze prognostic factors in patients with thoracic esophageal carcinoma staged pT1-4aN0M0 and undergone esophagectomy with 3-field lymphadenectomy and to evaluate the effect of postoperative radiotherapy.nnnMETHODSnFrom January 1993 to March 2007, 770 patients with stage pT1-4aN0M0 underwent 3-field lymphadenectomy at Fujian Province Cancer Hospital, China were enrolled for analysis. The study consisted of 770 patients with stage pT1-4aN0M0 who underwent 3-field lymphadenectomy at Fujian Province Cancer Hospital, China. A total of 687 had received surgery only, and 83 patients had undergone surgery followed by postoperative radiotherapy. Radiation dose was 50 Gy in 25 fractions.nnnRESULTSnThe overall survival rates at 1, 3, 5, and 10 years were 92.9%, 80.8%, 71.7% and 57.4%, respectively. Univariate analysis showed that age and T staging were two independent factors on prognoses. Five-year survival in cases younger and older than 60 were 76.5% vs. 63.3% (P=0.001), while those of pT1, pT2, pT3 and pT4a were 83.8%, 78.8%, 67.8% and 54.1%, respectively (P=0.000). Five-year survival in group of simple surgery was 71.3%, compared with 74.5% in group of surgery plus postoperative radiotherapy (P=0.763), while stratified analysis indicated that postoperative radiotherapy was able to boost the survival of patients in pT4a which were 72.4% vs. 33.8% (P=0.036) and to lower relapse rate of tumor bed in patients with pT4a (P=0.005). Multivariate analysis showed that age and T staging were two independent factors on prognoses.nnnCONCLUSIONSnPatients with high T staging and at an age more than 60 turned out bad prognoses, neither could postoperative radiotherapy improve their survival.

A new clinical staging system for esophageal cancer to predict survival after definitive chemoradiation or radiotherapy

This study is to evaluate the prognostic value of a new clinical staging system for esophageal cancer to predict survival after (chemo)radiotherapy. This retrospective study enrolled 444 patients with esophageal squamous cell carcinoma who underwent definitive intensity-modulated radiotherapy with or without chemotherapy between January 2008 and May 2014. A clinical staging system based on the gross tumor volume and maximum diameter of metastatic lymph nodes was developed and the prognostic value of this staging system was compared with that of the 8th edition of American Joint Committee on Cancer TNM staging system. The 3-year survival rate in the whole group was 44.5%. Multivariate analysis showed that gross tumor volume and maximum diameter of metastatic lymph nodes were independent prognostic factors. According to the proposed clinical staging system, the 3-year survival curves of each T, N, and TNM stage were well segregated. On the other hand, 3-year survival rates based on the 8th edition of cTNM staging system were similar between cT3 and cT4, cN1 and cN2, cN2, and cN3, III and IVa stages.The proposed clinical staging system appears to be a simple and accurate predictor of outcome in patients with esophageal squamous cell carcinoma who underwent definitive (chemo) intensity-modulated radiotherapy.

Patterns and rates of abdominal lymphatic metastasis following esophageal carcinoma

Aim To determine the rate of abdominal lymph node metastasis after radical surgery for esophageal cancer and define the radiotherapy target area. Methods Of the 1593 patients who underwent R0 radical esophagectomy for thoracic esophageal squamous cell carcinoma (TE-SCC), 148 developed abdominal lymph node (LN) metastases within three years of surgery. During that time interval, patients were examined by various imaging methods (enhanced computer tomography, magnetic resonance imaging, and positron emission tomography–CT) at set time points. The emerging recurrence pattern, preferred sites for abdominal metastasis, and correlation with added clinical factors were carefully recorded, to permit for delineation of a target area for radiotherapy. Results We found postoperative metastatic abdominal LNs in 9.3% of the patients treated for esophageal cancer. Lesions in the upper, middle, and lower esophageal segments metastasized to abdominal LNs at 2.3%, 7.8%, and 26.6% (P < 0.0001), respectively. Of all cases, 4.8% had fewer than two affected LNs, while 20.1% had more than three metastatic LNs (P< 0.0001). The metastasis rates of negative and positive celiac LNs were 4.6% and 22.7%, respectively. Abdominal LN metastasis rates for the following LNs: 16a2 and 16a1 of para-aortic, celiac artery, posterior surface of the pancreatic head and common hepatic artery were 64.9%, 41.2%, 37.8%, 32.4%, and 20.9%, respectively. The overall rate of metastasis to these groups of LNs was 91.9%. Conclusion This study determined that stations 16a1 and 16a2 of the para-aortic, truncus coeliacus, posterior surface of the pancreatic head, and arteria hepatica communis lymph nodes were the preferred sites for abdominal LN metastasis, thus defining target areas for postoperative radiotherapy.