3-year Distant Metastasis Rates Research Articles

The Impact of Radiation Dose on Preoperative Neoadjuvant Chemoradiotherapy Effects for Patients with Locally Advanced Squamous Cell Esophageal Carcinoma: A Propensity Score-Matched Retrospective Study.

Objective To explore the impact of radiation dose on preoperative neoadjuvant chemoradiotherapy effects for patients with locally advanced squamous cell esophageal carcinoma (LASCEC) with long-term follow-up data. Methods The patients with LASCEC received either low dose radiotherapy (50.4Gy/23f/1.8Gy) or a high dose (64.8Gy/25f/1.8Gy) followed by neoadjuvant chemotherapy preoperatively were included in this study. To balance potential bias, 1 : 1 propensity score matching (PSM) with a caliper of 0.1 was used. The two groups were compared in terms of radical resection, post-radiation adverse event rates, perioperative mortality, postoperative adverse event rates, overall survival (OS), local recurrence rate, and distant metastatic rate. Results Forty-two patients were enrolled in this study, with 21 patients in each group after PSM. There was no difference in baseline characteristics between the two groups (all p >0.05). The rates of radical resection (71.4% vs 57.1%, P =0.334), perioperative mortality (9.5% vs 4.8%, P =0.549), and postoperative adverse event rates (76.2% vs 90.5%, P =0.410) did not differ significantly between the two groups. The 5-year OS rate was statistically higher in the group with a high dose (66.7% vs. 28.6%, P =0.013). Meanwhile, the local recurrence rate was statistically lower in the high dose group (14.3% vs 47.6%, P =0.019 for 3 years; 33.3% vs 66.6%, P =0.031 for 5 years). Moreover, the 3-year distant metastasis rate was statistically lower in the group with a high dose (9.5% vs 38.1%, P = 0.03). Conclusion Patients with LASCEC may benefit from preoperative neoadjuvant chemoradiotherapy with a high radiation dosage (64.8Gy/25f/1.8Gy).

Increased rate of recurrence and high rate of salvage in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma with adverse features treated with primary surgery without recommended adjuvant therapy.

Some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline-recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS). Three-hundred and sixty-four patients with treatment-naïve, HPV-associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared. The 3-year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P < .001). Despite increased LRF, avoiding PORT was not associated with increased 3-year distant metastasis rates (8% vs 4%, P = .56) or worse 3-year survival (95% vs 98%, P = .34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged. Patients with HPV-associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates.

Prospective Clinical Study of Capecitabine plus Oxaliplatin Concurrent Chemoradiotherapy after Radical Resection of Rectal Cancer

To investigate the efficacy and safety of concurrent chemoradiotherapy with capecitabine or oxaliplatin in locally advanced (T3-4 / N + M0) rectal cancer. A total of 56 patients with rectal cancer after radical operation were randomly divided into group A: capecitabine + oxaliplatin concurrent chemoradiotherapy group (Cap-Oxa-CRT trial, 30 cases), group B: capecitabine concurrent chemoradiotherapy group (Cap-CRT trial as Control group, 26 cases), both groups were given pelvic radiotherapy DT50.4Gy/28f/6 weeks. The two groups received adjuvant chemotherapy after concurrent CRT. (1) The 3-year overall survival rate, 3-year local recurrence rate and 3-year distant metastasis rate were not significantly different between the two groups (P> 0.05). (2) The incidence of grade 1-2 acute toxicity in group A during concurrent CRT was significantly higher than that in group B, the difference was statistically significant (P <0.05). Grade 3 toxicities were not statistically significant between the two groups (P> 0.05). No grade 4 toxicity was found in both groups. The incidences of interrupted or suspend concurrent chemotherapy in both groups were 19.23% and 46.67%, respectively, P <0.05. The incidences of interruption or suspension of radiotherapy were 11.54% and 30% respectively (P> 0.05). The completion rate of adjuvant chemotherapy in group B was higher than that in group A, but the difference was not statistically significant (P> 0.05). In postoperative adjuvant chemotherapy, the incidence of bone marrow suppression in group A was higher than that in group B (P <0.05), and the incidence of non-hematologic adverse reactions was similar between the two groups. Capecitabine combined oxaliplatin concurrent CRT, and oxaliplatin concurrent CRT have a good effect for treatment of patients with locally advanced rectal cancer after radical resection of rectal cancer. However, group A failed to further improve the curative effect, and its grade 1-2 toxicity increased significantly.

Survival analysis of preoperative involved-field irradiation with concurrent chemotherapy for patients with Siewert′s type II and III adenocarcinoma of esophagogastric junction

Objective To analyze the clinical efficacy, toxicity and survival prognosis of patients diagnosed with Siewert type Ⅱ and Ⅲ locally advanced adenocarcinoma of esophagogastric junction (AEG) undergoing preoperative involved-field irradiation with concurrent chemotherapy. Methods A total of 45 cases were recruited in this prospective clinical trial. Prior to surgery, patients received 2 cycles of chemotherapy with XELOX and concurrent radiotherapy (a total of 45 Gy in 25 fractions, 5 times weekly). After 6-8 weeks, they underwent surgical resection. After the surgery, patients received 6 cycles of adjuvant chemotherapy. The completion of preoperative neoadjuvant chemoradiotherapy, postoperative pathological status, TNM down-staging effect and adverse reactions were observed. Kaplan-Meier method was applied to estimate survival analysis. Results All 45 patients completed preoperative neoadjuvant chemoradiotherapy. Among them, 39 patients completed 2 cycles of chemotherapy, and 6 patients completed 1 cycle of chemotherapy. The median time of surgical interval was 6 weeks. The R0 resection rate was 96%.The pathological complete response (pCR) rate was 22%. The TNM down-staging rate was 69%.The incidence of acute radiation-induced esophagitis or gastritis was 44% and the incidence of radiation-induced pneumonitis was 7%. The incidence of grade 1-3 leukocytopenia, thrombocytopenia and neutropenia was 78%, 47% and 44%, respectively. In terms of gastrointestinal reactions, the incidence of nausea, vomiting and loss of appetite was 62%, 24% and 71%, respectively. No hematologic or nonhematologic adverse effects was observed at grade 4 or 5.The median follow-up time was 30 months. 11 patients died of cancer, 1 patient was treatment-related death in the perioperative period and 1 patient died of pneumonia. The 1-, 2-and 3-year progression-free survival (PFS) rates were 90%, 70% and 67%, respectively. The 1-, 2-and 3-year overall survival rates were 95%, 80% and 75%, respectively. The 1-, 2-and 3-year local control rates were 95%, 84% and 84%, respectively. The 1-, 2-and 3-year distant metastasis rates were 7%, 25% and 25%, respectively. Conclusions Preoperative involved-field irradiation with concurrent chemotherapy yields relatively high clinical efficacy and is well tolerated by patients with Siewert type Ⅱ and Ⅲ locally advanced AEG.Patients are recommended to receive 4 cycles of adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery. Key words: Adenocarcinoma of esophagogastric junction/radiotherapy; Adenocarcinoma of esophagogastric junction/chemotherapy; Prognosis; Drug tolerance

P2.05-031 The Clinical Impact of Different Chemotherapy Regimen Combined with Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer: Topic: Multimodality Treatment

Different chemotherapy regimen have different toxicity for lung which regimen can improve the therapeutic effect and reduce the toxicity reaction have not reached a consensus. This was a retrospective study to evaluate the clinical toxicity reaction and therapeutic of different chemotherapy regimen combined with radiotherapy for the treatment of locally advanced non-small cell lung cancer (NSCLC). 117 non-small cell lung cancer patients were randomly dividedinto 3 groups,(1) group A (the patients received concurrent chemotherapy consisting of gemcitabine/cisplatin combined with radiotherapy), (2)group B (the patients received concurrent chemotherapy consisting of paclitaxel/cisplatin combined with radiotherapy) and (3) group 3 (the patients received the concurrent chemotherapy consisting of Changchun vinorelbine, irinotecan, pemetrexed or other chemotherapeuticdrugs/cisplatin combined with radiotherapy). All the patients received 2-4 cycles chemotherapy, and 2-2.2 Gy per fraction to a total of DT56-66 Gy thoracic radiotherapy 5 times per week. The overall response rate (CR+PR) of the three group was86.7%, 78.7%, 81.5% (x2=1.626, P=0.653). The 1-year, 2-year and 3-year progressionfree survival ratesof the three group were: 57.3%, 30.1%, 18.3%; 49%, 33.3%, 18.4% and 39.2%, 27.8%, 16.5% (x2=0.581, P=0.748). The 1-year, 2-year and 3-year overallsurvival rates were 89.3%, 48.5%, 30.3%; 65.5%, 43.3%, 26.8% and 70.3%, 48.3%, 31.6% (x2=1.658, P=0.437). The 1-year, 2-year and 3-year distant metastasis rates were 68%, 38.2%, 21%; 50.3%, 35.3%, 28.1% and 56%, 35.3%, 29.6% (x2=0.559, P=0.756). The incidence of radiation pneumonitis of the 3 group were: 37.5%、24%、20% (x2=4.909, P=0.037). In addition, the incidence of radiation esophagitis and bone marrow suppression in the three groups were 26.7%, 18.7%, 14.8 (P=0.832) and 26.7, 50.6%, 33.3%, (P=0.024). The patients received concurrent chemotherapy consisting of gemcitabine/cisplatin combined with radiotherapycould significantly increase the incidence of radiation pneumonitis, the patients received concurrent chemotherapy consisting of paclitaxel/cisplatin combined with radiotherapyalso had a high incidence of radiation pneumonitis. The local control rate and survival rate of the three groups were not statistically different.

Fluorouracil-based preoperative chemoradiotherapy with or without oxaliplatin for stage II/III rectal cancer: a 3-year follow-up study.

Fluorouracil-based preoperative chemoradiotherapy has become the standard treatment for stage II/III rectal cancer. In order to improve the overall survival (OS) and disease-free survival (DFS), we added oxaliplatin to the standard treatment, and compared the effectiveness of these two treatment patterns. A total of 206 patients enrolled in the prospective study had histologically confirmed rectal cancer of clinical stage II/III during July 2007 to July 2010. They were randomized into the experimental group received oxaliplatin and capecitabine in combination with radiotherapy, and the control group received capecitabine in combination with radiotherapy. All patients received surgery in 6-10 weeks after chemoradiotherapy and adjuvant chemotherapy with mFOLFOX6. The primary endpoints were DFS and OS, and the secondary endpoints included toxicity, compliance, and histopathological response. The 3-year OS in the experimental group and the control group was 90.29% vs. 86.41% (P>0.05), and the 3-year DFS was 80.58% vs. 69.90% (P>0.05). The pathological complete remission (pCR) rates were 23.30% and 19.42%, respectively (P=0.497). The 3-year local recurrence rates were 4.85% vs. 5.83% (P=0.694), and the 3-year distant metastasis rates were 16.50% and 28.16%, respectively (P=0.045). There were no significant differences in most grade 3-4 toxicities between two groups, however, grade 3-4 diarrhea occurred in 16.50% (17/103) of the experimental group, compared with 6.80% (7/103) of the control group (P=0.030). Also, the total grade 3-4 acute toxicity showed a significant difference (10.68% vs. 21.36%, P=0.037). The experimental treatment did not lead significantly improved OS and DFS, and thus longer follow-up is warranted for our patient cohort. Adding oxaliplatin to capecitabine-based preoperative chemoradiotherapy can significantly reduce metastasis, but has only minimal impact on local recurrence. Although grade 3-4 toxicity rate increased (primarily gastrointestinal toxicity), patients can stand to be followed up with allopathic treatment.

胃癌根治术后辅助治疗的临床分析

目的：分析胃癌根治术后辅助治疗的疗效和副作用。方法：2005年1月至2012年9月在本院接受综合治疗的患者，男性94例，女性62例，平均年龄58.2岁(23~84岁，中位58岁)。所有病例均为手术病理证实为胃癌，按AJCC分期第7版标准，IA期7例，IB期7例，IIA期6例，IIB期19例，IIIA25例，IIIB期34例，IIIC期44例，IV期12例，不详2例。156例均采用根治性切除。12例术后未行任何化疗，142例术后接受各种方案的化疗，其中64例采用多西紫杉醇 + 铂类 + 氟尿嘧啶类(DCF)或表阿霉素 + 铂类 + 氟尿嘧啶类(ECF)三药方案，66例采用铂类 + 氟尿嘧啶类两药方案，9例采用口服替吉奥或卡培他滨单药化疗，1例仅采用铂类 + 氟尿嘧啶类腹腔灌注，2例化疗方案不详。有28例接受术后放疗。结果：中位随访36.5月。3年总生存率为53.5%，3年局部控制率为82.0%，3年无远处转移率53.8%。单因素分析显示T分期(T1-3或T4)、N分期(N0-1或N2-3)、术后分期(I-II期或III-IV期)与总生存和局部控制有统计学意义，而淋巴管癌浸润(浸润或否)影响远处转移。另外，在术后化疗方面，采用三药方案的在总生存上优于两药方案(P=0.047)。结论：胃癌总体疗效仍不高，术后化疗采用DCF/ECF三药方案OS可能有优势。 Objective: To analyze the response and side effects of postoperative adjuvant therapy in gastric cancer. Methods: From January 2005 to September 2012, 156 patients with gastic cancinoma re-ceived the treatment in our hospital, 94 male, 62 female. The average age is 58.2 years (23 to 84 years, median 58 years). All the cases were pathologically confirmed gastric cancer. According to the 7th edition AJCC staging, IA, 7 cases; IB, 7 cases; IIA, 6 cases; IIB, 19 cases; IIIA, 25 cases; IIIB, 34 cases; IIIC, 44 cases; IV, 12 cases; 2 cases were unknown. All 156 cases have adopted radical resection. 12 cases did not undergo any chemotherapy after surgery; 142 cases received postoperative chemotherapy, 64 cases were treated with docetaxel + platinum + fluorouracil (DCF) or epirubicin + platinum + fluorouracil (ECF) three-drug regimen; 66 cases were treated with platinum + fluorouracil two-drug regimen; 9 cases with oral S1 or capecitabine chemotherapy; one case with only intraperitoneal infusion of platinum + fluorouracil; two cases, unknown chemotherapy regimen. 28 patients received postoperative radiotherapy. Results: The median follow-up was 36.5 months. 3-year overall survival rate was 53.5%; 3-year local control rate was 82.0%; 3-year distant metastasis rate was 53.8%. Univariate analysis showed that T stage (T1-3 or T4), N stage (N0-1 or N2-3), postoperative stage (I-II or III-IV) were statistically significant with local control and overall survival (P < 0.05 for all) and that lymphatic invasion had impact on distant metastasis (P=0.036). In postoperative chemotherapy, the use of three-drug regimen is superior to the two-drug regimen on overall survival (P=0.047). Conclusions: The overall effect of treatment in gastric cancer remains poor. Postoperative chemotherapy using DCF/ECF three-drug regimen might have an advantage on overall survival.

Value of postoperative adjuvant chemotherapy in locally advanced rectal cancer patients with ypT1-4N0 after neo-adjuvant chemoradiotherapy

The purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy. We performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases. The median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548). Adjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.

Cisplatin/etoposide chemotherapy combined with twice daily thoracic radiotherapy for limited small-cell lung cancer: A clinical Phase II trial

To fit the situation of developing countries, where supportive care is not sufficient, a modified combined therapy of cisplatin/etoposide (EP) and hyperfractionated accelerated radiation therapy (HART) was conducted as a Phase II trial for limited-stage small-cell lung cancer (LSCLC) to evaluate the feasibility, toxicity, and tolerance of the combined therapy and to observe its efficacy and patterns of failure. Chemotherapy and radiation were sequentially administered in 1 to 3 cycles before and 3 to 5 cycles after HART. Chemotherapy contained cisplatin in doses of 25 to 30 mg/m(2) from Day 1 to Day 3 and etoposide in doses of 50 to 70 mg/m(2) from Day 1 to Day 3. The HART schedule consisted of radiation delivered in 1.4-Gy fractions, twice a day, at intervals longer than 6 h for 5 treatment days a week, to a total dose of 56 Gy in 40 fractions over 4 weeks. From June 1997 to December 2000, 57 eligible patients were registered for this trial. All were limited stage, and the median age was 60 years (range, 25 to 70 years). Of the 57 patients, 3 were withdrawn because of distant metastases (1 case), Grade (Gr) III thrombocytopenia (1 case), and financial problems (1 case). Fifty-four patients completed the planned combined treatment. A median of 6 cycles of chemotherapy (range, 5-8 cycles) was administered during a median interval of 4.9 weeks (range, 3.0-8.9 weeks), and a radiation dose of 56 Gy in 40 fractions was delivered over 29 days. The most common acute complication was radiation esophagitis, which occurred in 41 cases (72%), 4 with Gr III. Thirty-six patients (64%) had acute pulmonary toxicity, 2 with Gr III. The median survival time was 24 months (95% CI, 21-28 months). The 1-year, 2-year, and 3-year survival rates were 81% (95% CI, 70%-91%), 49% (95% CI, 36%-62%), and 21% (95% CI, 10%-32%), respectively. Of 57 patients, 13 had locoregional progression. Nine patients failed inside radiation fields and 4 patients failed outside. The 1-year, 2-year, and 3-year locoregional progression-free survival rates were 85% (95% CI, 75%-95%), 74% (95% CI, 61%-87%), and 68% (95% CI, 52%-84%), respectively. Forty-four patients suffered distant metastases, 66% of which were in brain. The 1-year, 2-year, and 3-year distant metastasis rates were 31% (95% CI, 19%-43%), 59% (95% CI, 46%-72%), and 79% (95% CI, 68%-91%), respectively. The study led to the following conclusions: (1) LSCLC patients tolerate HART at 56 Gy in 40 fractions over 4 weeks combined with 6 cycles of EP chemotherapy. (2) Both control of the tumor in the thorax and survival appear superior to conventional fractionated radiation but not as good as that in a study by Turrisi and colleagues. (3) This modified chemoradiation schedule could be recommended to LSCLC patients in developing countries. (4) The lessons learned from our study are (a) higher radiation doses may be needed for better locoregional control, and (b) prophylactic cranial irradiation is necessary for LSCLC patients who show complete response.

Hyperfractionated accelerated radiation therapy for nonsmall cell lung cancer: Clinical phase [formula omitted] trial

In an attempt to improve local control and survival of nonsmall cell lung cancer (NSCLC), hyperfractionated accelerated radiation therapy (HART) was carried out as a clinical phase I/II trial. HART was delivered by 1.1 Gy/fraction, three fractions per day with intervals of 4 h and five treatment days per week. The clinical tumors were irradiated to 74.3 Gy (72.6-75.9)/66-69 fx, 33 days (29-40) (not corrected for lung density), and the subclinical lesions, to 50.0 Gy (48.4-50.6)/44-46 fx, 33 days (29-40). Sixty-nine patients with NSCLC were enrolled in this study. Nine patients were withdrawn from the study during HART due to different reasons. Sixty patients formed the study for outcome analyses. They were 57 males and 3 females with median age of 61 years (21-77). There were 41 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 4 cases of large cell carcinoma. Overall, favorable patients (KPS > or = 70, weight loss < 5% and Stages I, II, IIIa) accounted for 73% (44 of 60) of all patients. Forty-four patients (73%) received adjuvant chemotherapy (DDP + VP16) with median cycles of 1.8 before and/or after HART. In order to compare the outcome of HART with conventional irradiation, 50 NSCLC patients treated by conventional fractionated irradiation (CFI) during the same period were chosen as the basis to evaluate relative effects of HART. They derived from the control group of another clinical trial of hyperfractionated irradiation for NSCLC in the same department. They received median tumor dose of 63.9 Gy (62.8-65.0)/34 fx (32-36), 48 days (45-53). 1. Acute and late complications: (a) In HART, 87% of patients (52 cases) developed acute radiation esophagitis: Grade 1-2, 46 cases (77%) and Grade 3, 6 cases (10%), at 2.5 weeks (2-3.5 weeks) after HART began. Five patients with Grade 3 esophagitis had their HART interrupted for <7 days. In CFI, esophagitis was much less (44%,p < 0.05) with 38% of Grade 1-2 and 6% of Grade 3. (b) In HART, acute pulmonary symptoms (RTOG Grade 1-2) occurred in 17% (10 cases), and acute radiation pneumonitis (Grade 3), in 8% (5 cases), while in CFI, they were 24% and 2% (p > 0.05), respectively. Late lung fibrosis (RTOG Grade 1-2) appeared in 20% (12 cases), whereas 18% in CFI (p > 0.05). (c), No other severe acute or late complications have been observed so far in HART. 2. Immediate response. In HART, 20% of patients (12 cases) achieved CR, 60% (36 cases), PR and 20% (12 cases), NR or PD. In CFI, the above three percentages were 10, 28, and 62%, respectively (p < 0.001). 3. Follow-up. The 1-, 2-, and 3-year actuarial survivals were 72, 47, and 28% for HART, and 60, 18, and 6% for CFI, respectively (p < 0.001). Better local control was seen in HART than in CFI with 1-, 2-, and 3-year local control rates being 71, 44, 29%, and 60, 20, and 5%, respectively (p = 0.001). Distant metastases developed less in HART than in CFI. The 1-, 2-, and 3-year distant metastasis rates were 23, 36, and 50% in HART, but 30, 48, and 80% in CFI (p = 0.021). 1. HART could be tolerated by most of the favorable NSCLC patients. The predominant complication was acute esophagitis. No other severe acute or late complications have been observed so far. 2. HART resulted in better survivals and local controls, and less distant metastases than CFI.