Is D2 Lymphadenectomy Alone Suitable for Gastric Cancer With Bulky N2 and/or Para-Aortic Lymph Node Metastases After Preoperative Chemotherapy?

BackgroundFor gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT.MethodsWe retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study.ResultsFrom May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%).ConclusionThe results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT.

Neoadjuvant chemotherapy plus surgery for high-risk advanced gastric cancer: Long-term results of KDOG1001 trial.

4521 Background: In the phase 2, open-label, KDOG1001 (UMIN000003642) study, neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and S-1 (DCS), followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer showed feasibility of DCS therapy with an enough R0 resection rate of 90%. Here we present long-term results after a minimum follow-up of 3 years. Methods: Patients with bulky node metastasis (bulky N), linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy. This analysis presents the final preplanned assessment of outcomes after 3 years. Primary endpoint was R0 resection rate. Secondary endpoints included overall survival (OS), progression free survival (PFS), completion rate of the protocol treatment, and pathological response rate (pRR) of DCS NAC. Results: Of 40 patients enrolled from May 2010 through January 2017, 7 (17.5%) had bulky N, 18 (45.0%) had type 4, and 16 (40%) had large type 3 with 1 (2.5%) having both large type 3 and bulky N2. All included patients underwent preoperative DCS chemotherapy followed by surgery with D2 lymphadenectomy with 32 (80%) completed postoperative S-1 therapy for 1 year. After a median follow-up for surviving patients of 67 mo (range, 36 mo to 110 mo) at the last follow-up in January 2020, 3-year OS was 78% [95% confidence interval (CI) 62–88%], while 3-year PFS was 63% (95% CI 47–76%). Completion rate of the protocol treatment was 62.5% (25/40) with pRR of 57.5% (23/40). In bulky N2, 3-y OS was 86% and 3-y PFS was 71% with pRR of 100%. In type 4, 3-y OS was 67% and 3-y PFS was 50% with pRR of 44%. In large type 3, 3-y OS was 88% and 3-y PFS was 75% with pRR of 56%. Patients with type 4 had significantly worse OS and PFS than those with the other types [HR 7.20 (95% CI 2.23–32.21) and HR 3.00 (95% CI 1.21–8.19)]. Conclusions: Preoperative chemotherapy with up to four cycles of DCS followed by gastrectomy plus adjuvant S-1 therapy is a promising treatment strategy for patients with bulky node metastasis, type 4 and large type 3 gastric cancers. For type 4 cancer, further improvement of treatment strategy is needed. Clinical trial information: 000003642 .

Thoracoscopic Surgery Shows Non-Inferiority to Open Surgery for Clinical N0-N2 and Pathologic N2 Non-Small Cell Lung Cancer

Objectives Controversy has remained over the primary surgical management for stage IIIA-N2 non–small cell lung cancer. Minimal or non-bulky N2 disease defined as single-station nodal involvement may still be a candidate of radical surgery. The aim of this study was thus to assess the outcome of thoracoscopic surgery in clinical N0-N2 and pathologic N2 disease. Methods Seventy-nine cases of pathologic N2 diseases without induction therapy (clinical N0, 27; N1, 13; N2, 39) were operated on between September 2003 and December 2010 in our institute. Forty-seven patients underwent thoracoscopic surgery (group T) and 32 patients underwent standard thoracotomy (group S). Perioperative and oncologic outcomes were compared between the 2 groups. Results There were no significant differences between the 2 groups regarding dissected number of lymph nodes, operative time, morbidity, and mortality. However, blood loss in group T was less than in group S (Mean: T, 229 versus S, 534 mL, respectively; P = 0.0004). Although disease-free survival in group T did not differ from that in group S, overall survival in group T was better than in group S after propensity score matching to adjust confounding factors including tumor size and T factor (P = 0.03). Multivariate analysis showed that multinodal stations was significantly worse prognostic factor [hazard ratio (HR) = 4.79; 95% confidence interval (CI) = (1.6–14.3); P = 0.005) in disease-free and overall survivals [HR = 8.21; 95% CI = (1.9–35.4); P = 0.005]. Thoracoscopic surgery was favorable prognostic factor in overall survivals [HR = 0.13; 95% CI = (0.03–0.6); P = 0.009]. Conclusions Our study demonstrated that thoracoscopic surgery for non-bulky N2 disease was feasible and not inferior to standard thoracotomy in terms of oncologic outcome.

Outcomes of occult primary (OP) of the head and neck squamous cell carcinoma (HNSCC) treated with oropharynx (OPX)-targeted radiotherapy (RT) and concurrent chemotherapy (CCRT).

5559 Background: OP of HNSCC is commonly treated with comprehensive mucosal RT including nasopharynx, OPX, hypopharynx and larynx and bilateral neck. We are reporting the long term outcomes of a conservative mucosal sparing technique consisting of targeting only the OPX mucosa and bilateral necks. Methods: This is a single-institution retrospective study. From January 1998-2010, a total of 68 patients with OP of HNSCC were treated with CCRT (90%) or RT alone (10%), 40% with IMRT. RT fields comprehended OPX mucosa only and bilateral necks. Gross disease in the neck received 70Gy, involved neck 63 Gy, OPX 60 Gy, uninvolved neck and ipsilateral retropharyngeal nodes 54 Gy. All fractions were given at the rate of 1.8-2 Gy/fraction. The median age was 58 (21-87), 80% Caucasian, and 75% males. Stage IVa (N2) was 75% of the population, while stages III (N1), and IVb (N3) were 9, and 16% respectively. 16 patients (9N3+7 bulky N2) underwent neck dissection (ND). The median time interval from diagnosis to RT and RT duration were 60 (13-70) and 50 days (49-63) respectively. The Median number of Chemotherapy cycles was 2 (1-3). Cisplatin was given to 70% of pts, while Carboplatin and Cetuximab were 10 and 20% respectively. Results: With a median follow-up of 5.3 years (1– 13.6), the loco-regional control, (LRC) for all stages is 95.6 %. The median time to LRF is 18 months (12 - 63). Chronic CCRT toxicity was; grade (1) xerostomia (67%), dysphagia (35%), altered taste (28%), neck stiffness (15%), skin toxicity (12%), dysphonia (9%), and trismus (6%). One HIV patient developed grade 4 dysphagia. No patients experienced distant metastases. The emergence of primary was (1.5%) 1 patient developed subglottic SCC 2 years after CCRT, 2 patients failed in the neck (originally N3) all the 3 patients were salvaged successfully by surgery. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100. Conclusions: Our data show that CCRT or definitive RT alone to the OPX and bilateral neck provides excellent oncologic and functional outcomes. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable and likely reduces toxicity.

Induction Therapy for Poor-Prognosis Anal Canal Carcinoma: A Phase II Study of the Cancer and Leukemia Group B (CALGB 9281)

PurposeAlthough most patients with anal canal cancer are cured with sphincter-preserving, nonsurgical, combined-modality therapy, those with large tumors and lymph node involvement have a poor prognosis. To establish the safety and efficacy of induction chemotherapy with infusional fluorouracil (FU) plus cisplatin followed by FU plus mitomycin C with concurrent radiation in patients with poor-prognosis squamous cell cancers of the anal canal.MethodsPatients with previously untreated anal canal cancers with T3 or T4 tumors and/or extensive nodal involvement (bulky N2 or N3) received two 28-day cycles of induction treatment with infusional FU plus cisplatin followed by two 28-day cycles of FU plus mitomycin C with concurrent split-course radiation. A third cycle of FU and cisplatin with radiation boost was given to patients with persistent primary site disease or bulky N2 or N3 disease at presentation.ResultsForty-five assessable patients received protocol therapy. Treatment was generally well tolerated, and gastrointestinal and hematologic toxicities were the most common. Induction chemotherapy resulted in eight complete and 21 partial responses. After induction, combined-modality, and boost therapy, 37 (82%) of 45 assessable high-risk patients achieved a complete response. After 4 years of follow-up, 68% of patients are alive, 61% are disease-free, and 50% are colostomy- and disease-free.ConclusionA combined-modality approach that includes induction treatment with FU and cisplatin followed by combined-modality therapy with FU, mitomycin C, and concurrent radiation results in long-term disease control in the majority of patients with poor-prognosis anal canal cancer.