Induction Chemotherapy Group Research Articles

Propensity-matched analysis of three different chemotherapy sequences in patients with locoregionally advanced nasopharyngeal carcinoma treated using intensity-modulated radiotherapy.

BackgroundTo compare the survival outcomes and acute toxicities of concurrent chemoradiotherapy (CCRT), induction chemotherapy (IC) plus radiotherapy (RT), and IC plus CCRT in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiotherapy (IMRT).MethodsPatients with stage III–IVB NPC who were treated with IMRT between 2009 and 2012 at a single institution were retrospectively reviewed. The induction regimens included PF (cisplatin and fluorouracil) and TP (docetaxel and cisplatin) every 3 weeks for 2–3 cycles; the concurrent regimen was cisplatin every three weeks for 2–3 cycles. A propensity score matching method was used to match patients from each group in a 1:1:1 ratio.ResultsIn total, 147 eligible patients were propensity-matched, with 49 patients in each treatment group. The median follow-up duration was 38.5 months (range, 4.5 – 56 months). The 3-year disease-free survival, overall survival, distant metastasis-free survival, and locoregional relapse-free survival rates were 82.1 %, 92.8 %, 87 %, and 90.4 % in the CCRT group; 86.3 %, 91.0 %, 91.6 %, and 94.4 % in the IC plus RT group; and 87.8 %, 95.8 %, 93.8 %, and 93.9 % in the IC plus CCRT group, respectively. No statistically significant survival differences were observed between the three treatment groups in either univariate or multivariate analyses. The incidence of grade 3–4 acute toxicities was similar among groups.ConclusionsThis study suggests that CCRT, IC plus RT, and IC plus CCRT are similarly efficacious treatment strategies for patients with locoregionally advanced NPC treated using IMRT; however, long-term, large-scale randomized trials are required to confirm these findings.

Can induction chemotherapy before concurrent chemoradiation impact circumferential resection margin positivity and survival in low rectal cancers?

Distance from anal verge and abdominoperineal resection are risk factors for circumferential resection margin (CRM) positivity in rectal cancer. Induction chemotherapy (IC) before concurrent chemoradiation (CRT) has emerged as a new treatment modification. Impact of IC before concurrent CRT on CRM positivity in low rectal cancer remains to be independently studied. The objective of this study was to determine CRM positivity in low rectal cancer, with and without prior IC, and to identify predictors of disease free and overall survival. Patients who underwent surgery for rectal cancer between 2005 and 2011 were retrospectively reviewed and divided into two groups. Group 1 received IC before CRT and Group 2 did not. Demographics, clinicopathological variables and CRM status were compared. Actuarial 5 year disease free survival (DFS), overall survival (OS) and independent predictors of survival were determined. Patients in the IC group presented with advanced stage (Stage 3=89.2% versus 75.4%) (P=0.02) but a high rate of total mesorectal excision (TME) (100% versus 93.4%) (P=0.01) and sphincter preservation surgery (54.9 % versus 22.9%) (P=0.001). Patients with low rectal cancer who received IC had a significantly low positive CRM rate (9.2% versus 34%) (P=0.002). Actuarial 5 year DFS in IC and no IC groups were 39% and 43% (P=0.9) and 5 year OS were 70% and 47% (P=0.003). Pathological tumor size [HR: 2.2, CI: 1.1-4.5, P=0.01] and nodal involvement [HR: 2, CI: 1.08-4, P=0.02] were independent predictors of relapse while pathological nodal involvement [HR: 2.6, CI: 1.3-4.9, P=0.003] and IC [HR: 0.7, CI: 0.5-0.9, P=0.02] were independent predictors of death. In low rectal cancer, induction chemotherapy before CRT may significantly decrease CRM positivity and improve 5 year overall survival.

Retrospective Study of Induction Chemotherapy and Concurrent Chemoradiation Therapy for Oropharyngeal Cancer

We carried out this study to clarify the treatment outcomes and problems associated with induction chemotherapy (using taxotere, cisplatin and 5-FU [TPF therapy]) and chemoradiotherapy in patients with oropharyngeal cancer. The data of 44 patients receiving their initial treatment for oropharyngeal cancer (including 2, 9 and 33 patients with stage II, stage III and stage IV disease, respectively, and 31, 8 and 3 patients with side wall, front wall and upper wall (soft palate and uvula) involvement) were examined. Of the 44 patients, 33 received induction chemotherapy and 11 received chemoradiotherapy. The feasibility, incidence of neutropenia, response rate, and 3 year disease-specific survival rate in the induction chemotherapy group vs. chemoradiotherapy group were 70%, 88%, 82% and 73%, respectively, vs. 63%, 91%, 82% and 55%, respectively. A statistically significant difference in the 3-year disease-specific survival rate was seen between the p16-positive and p16-negative patients in the induction chemotherapy group: while the rate was 100% in the p16-positive patients, it was only 51% in the p16-negative patients (p=0.004). Of the patients undergoing chemoradiotherapy, 3 developed mandibular osteomyelitis, which was considered as one of the important problems associated with this therapy.

Up-Front Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Arising from the Myelodysplastic Syndrome

In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available. © 2014 S. Karger AG, Basel

712P - A Three-Step Strategy of Induction Chemotherapy, Chemo-Radiotherapy and Surgery in Locally Advanced Pancreatic Cancer (Lapc) Patients. Role of a Nonlinear Mixed Effects Modeling to Predict Outcome

ABSTRACT Aim: The optimal strategy for patients with LAPC remain a therapeutic challenge. A growing evidence suggests that both, pts with borderline resectable and unresectable tumors may benefit from a multimodal approach aimed at improving resectability and survival times. In the present work our experience after a long-term follow-up period is reported. Methods: From December 2005 to July 2011, 67 histologically confirmed LAPC, endoscopic ultrasound (EUS) staged T3-4 and/or N+ were retrospectively analysed. They received induction gemcitabine/oxaliplatin- based chemotherapy followed, in case of radiological response or stable disease, by chemo-radiotherapy (50.4 Gy concurrently with daily capecitabine and weekly oxaliplatin). Salvage surgery was performed when technically feasible. We have applied a nonlinear mixed effects (NLME) modeling to evaluate the impact of dynamic changes in tumor size, Ca- 19.9, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio on the clinical outcome of these patients. Results: The median age was 63 years (range 35-85). Male to female 36/31. Thirty eight pts (57%) completed the whole program (group A), whereas 27 (40%) received chemo and radioterapy but were not elegible for surgery (Group B). Two pts (3%) progressed after induction chemotherapy (Group C). EUS staged T4 or N+ was found in 20 (30%) and 24 (36%) respectively. Toxicity profile was mild, with no grade 4 toxicity being documented. On an intent to treat basis, R0 resection rate was 57%; ypT0ypN0 were observed in 11 (29%) of patients. Among resected patients, local and distant failure rates were 5% and 55%, respectively. The liver was the most frequent site of relapse 21(43%) pts. After a median follow up of 23 months (range 4 to 102), median PFS was 21, 10 and 1 month in groups A, B and C respectively (p = Conclusions: Our date suggest that this three-step strategy is feasible and active in LAPC patients. The NMLE population modeling will be presented at the meeting Disclosure: All authors have declared no conflicts of interest.

Analysis of efficacy and prognosis of induction chemotherapy in 76 elderly patients with acute myeloid leukemia (non-APL)

This study was purposed to investigate the clinical features, diagnosis, treatment and prognosis of elderly patients with acute myeloid leukemia (AML) (non-APL). The clinical data of 76 elderly ( ≥ 60 old years) AML (non-APL) patients from January 2000 to January 2010 were analyzed retrospectively. According to treatment methods,the 76 patients were divided into 2 groups: induction chemotherapy group (51 cases) and best supportive treatment group (25 cases). The patients in induction chemotherapy group received the cytarabine-based induction chemotherapy regimens, including DA, MA, HA, IA and CAG; the patients in best supportive treatment group received supportive treatment including hydroxyurea, blood transfusion and so on. The clinical features, diagnosis, treatment and prognosis between 2 groups were compared. The results showed that the median survival times of patients in induction chemotherapy and best supportive treatment groups were 5 (0.2-89) and 3 (0.1-17) months respectively, there was significantly statistical difference in median survival time between 2 groups(P < 0.01) suggesting that the induction chemotherapy obviously prolonged the survival time of elderly CML patients. The 5 patients in induction chemotherapy group survived more than 60 months, one of them survived more than nine years. After the first cycle of chemotherapy, the complete remission (CR) rate of patients was 19.6% (10/51), partial remission (PR) rate was 19.6% (10/51), the overall response rate (ORR) was 39.2%, the mortality of patients in induction remission stage was 13.7% (7/51) in induction chemotherapy group; no 1 case in best supportive treatment group reached to CR. The CR rate of patients by using MA regimen was 44.4% and its ORR was 55.5%, which was higher than that by using DA, HA, IA and CAG regimens. The median chemotherapy cycles were 3 (1-14). The follow-up found that the 3 months-survival rate of patients was 65% and 42%, the 6 month-survival rate of patients was 43% and 21%, the 1 year-survival rate of patients was 29% and 13%, the 5 year-survival rate of patients was 13% and 0% in induction chemotherapy and best supportive treatment groups respectively, showing that the survival of patients in induction chemotherapy group was better than those in best supportive treatment group. A total of 31 of out 51 cases (60.8%) in induction chemotherapy group not response to the first cycle of chemotherapy, the survival time of these patients was not statistically significantly different from that of patients in best supportive treatment group. It is concluded that the induction chemotherapy can significantly improve the prognosis of elderly patients with AML, and prolong their median survival time. The induction remission rate in elderly patients with AML is lower than that of younger patients. The MA regimen is better than DA, HA, IA and CAG, there is individual difference in the elderly patients with AML, If the first cycle of chemotherapy has not reached to CR or PR, the best supportive treatment may be considered. The low toxicity, efficient and well-tolerated chemotherapy regimens may be chosen to prolong the survival time of the elderly patients with AML (non-APL).

Effect of induction chemotherapy (IC) on survival in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with chemoradiotherapy: Single center experience.

e17032 Background: Eventhough IC can lower distant metastasis rates in LA-HNSCC, survival benefit of IC has not yet been confirmed. We evaluated whether IC prior to concurrent chemoradiotherapy (CCRT) improves overall survival comparing with CCRT alone. Methods: Medical records were retrospectively reviewed for 224 patients who were diagnosed of LA-HNSCC from January 2005 to January 2013. We analyzed overall survival (OS) and progression-free survival (PFS) between the patients who received IC followed by CCRT (N=144) and CCRT alone (N=80). Results: Of total 224 patients, 195 were male. Median age was 61.0 years old. Sites of disease were as follows: oropharynx= 101; hypopharynx= 42; larynx= 23; oral cavity= 32; nasal cavity= 6; and others= 20. Among the IC group, 71 patients (49.3%) had received docetaxel plus cisplatin as IC regimen. Of all patients, 199 patients (88.9%) had CCRT with weekly cisplatin. The median follow-up duration was 48.5 months (range 13.8-100.6 months). Three year OS rate was signif...

Traitements néoadjuvants : évaluation d’une pratique couramment indiquée en RCP

The management of localized non-small cell lung cancer (NSCLC) has been modified over the last decades, with induction therapies being increasingly recommended as a prerequisite to surgical resection. However, the relative impact of chemo- and chemoradiotherapy on tumours' pathology and patients' survival is still discussed. We set a retrospective study including every patient who underwent surgical resection for NSCLC in 2 French centres from 1980 to 2009. We then compared the tumours' pathology and patients' survival according to the use of induction chemotherapy (group 1) or induction chemoradiotherapy (group 2). There were 733 patients in group 1 and 126 patients in group 2. In group 1, 669 patients (91%) had platinum-based chemotherapy, for 2 to 3 cycles in 564 cases (77%). In group 2, chemoradiotheray was concomitant in 68 patients (54%), and sequential in 58 patients (46%). As compared with group 1, group 2 was characterized by younger age (mean 59.8±9.5 vs 56.4±9.6, respectively, P<.001), a higher rate of tumours deemed unresectable before induction treatment (25% vs 44%, P<.001), and a higher proportion of T4 (25% vs 44%, P<.001) or N2 diseases (56% vs 69%, P=.005). The type of resection, postoperative complications, and postoperative mortality were not significantly different between groups. On final pathologic report, as compared with group 1, there were more N0 and N1 disease in group 2 (N0: 43% vs 58%, P=.002; N1: 22% vs 10%, P=.002) while the rate of N2 disease was comparable (34% vs 32%, P=ns). The median, 5-, and 10-year survivals were 28 months, 35%, and 21% for group 1, and 29 months, 36%, and 23% for group 2, respectively (P=ns). As compared with induction chemotherapy, induction chemoradiotherapy was performed in more advanced NSCLC, and resulted in better downstaging, similar postoperative course, and comparable long-term outcome after surgical resection.

A Single Institution Experience With Induction Chemotherapy (ICT) Followed by Chemoradiation (CRT) Versus CRT for Definitive Treatment of Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-SCCHN)

the 13 patients who developed DM, the LN levels involved were: Level I (3 pts), Level II (12 pts), Level III (8 pts), Level IV (7 pts), Level V (6 pts) and RP group (2 pts). Hence, the risk of DM stratified based on each LN level was calculated as follows: Level I (33%), Level II (20%), Level III (20%), Level IV (39%), Level V (46%) and RP group (33%). The 3 patients with DM who had Level I LN involved had extra-oral cavity primaries with multi-level involvement (Supraglottic Larynx “level I-V”, Base of Tongue ”Levels I,III,IV” and Tonsil “Level I-II”). The most common site for DM was lung (8 pts), followed by bones (5), liver (2) and brain (1). Conclusions: Patients with HNSCC who have involved Lymph Node levels IV, V or RP group are associated with 33-46% risk of DM on this cohort and should be considered to be further assessed for the role of adjuvant systemic therapy. Author Disclosure: H. AlHussain: None. I. Busca: None. L. Eapen: None. S. El-Sayed: None.

WS14-5 - Management of Advanced Testicular Cancer

ABSTRACT Introduction Though eighty percent of advanced germ cell tumors (GCTs) could be cured to date, only 20–30% of patients with chemotherapy refractory or resistant GCTs, so called ‘difficult-to-treat’ GCTs would remain continuously disease-free with salvage chemotherapy or surgery. International classification gave us to the information about induction and second-line chemotherapy, however, the optimal salvage chemotherapy remains unclear. In this session, we will review literatures and present our sequential chemotherapy strategy for advanced GCTs. Patients and methods Two hundred sixteen patients with advanced GCTs treated at Kyoto Prefectural University of Medicine from June 1998 to December 2011 were retrospectively assessed. Results Median age was 32 years (range: 17–68 years). Non-seminoma was in 181 cases (83.8%), regarding primary histology. IGCCC showed good in 94 cases (45.2%), intermediate 58 (27.9%), poor 56 (26.9%). As the induction therapy, BEP therapy was carried out in 190 cases (88.0%). Salvage chemotherapy was done for 121 cases. As the second-line therapy, VIP/VeIP and TIP/N therapy were done in 42 (34.7%) and 41 cases (33.8%), respectively. Regarding the patients requiring third line or more chemotherapy, 90, 61, 39, 23 cases had third, fourth, fifth and sixth line or more chemotherapy, respectively. Irinotecan-containing chemotherapy was done in 22 cases and 35 cased as second- + third-line therapy and fourth line or more, respectively. Gemcitabine-containing therapy was done in 35 cases with fourth line or more chemotherapy. The overall survival rate at median follow-up period was 95.7% in induction chemotherapy group (median follow-up; 53 months) and 69.2% in salvage chemotherapy group (median follow-up; 47 months). Clinical outcomes showed no evidence of disease (NED) was obtained in 91.5% and 90.3% with induction and second-line therapy, respectively. Noteworthy mentioned, about 40% patients had NED even in the fourth line or more chemotherapy group. Conclusion Very good and relatively good prognosis were obtained in the patients with induction and salvage chemotherapy at high volume center, respectively. Sequential continuous chemotherapy would be very important to manage ‘difficult-to-treat’ advanced germ cell tumors.

718P - A Three-Step Strategy of Induction Chemotherapy, Chemo-Radiotherapy and Surgery in Locally advanced Pancreatic Cancer (LAPC). A Single Institutional Experience

ABSTRACT Background Pancreatic cancer is one of the most highly fatal cancers. A growing evidence suggests that even potentially resectable patients (pts) benefit from a multidisciplinary approach aimed to improve resectability and reduce recurrence. We report our experience after a long-term follow-up. Methods From December 2005 to July 2011, 69 histologically confirmed LAPC, endoscopic ultrasound (EUS) staged T3/T4, N0/N1 were scheduled to receive induction gemcitabine-oxaliplatin-based chemotherapy followed by chemo-radiotherapy with weekly oxaliplatin and capecitabine (mean radiotherapy dose of 50.4 Gys) and salvage surgery when feasible. Adjuvant chemotherapy was considered depending on results of the pathologic report. Results The median age was 63 years (range 35-83 years). Male to female ratio was 37/32. Forty-one pts (59%) completed the whole program (group A), whereas 26 (37%) received chemo and chemo-radiotherapy but were not eligible for surgery (group B). Two patients (3%) progressed after induction chemotherapy (group C). Endoscopic stent placement was performed in thirty-four pts (49%). Toxicity profile was mild, with no grade 4 toxicity being documented. Grade 3 toxicity included: leucopenia (7%), neutropenia (11%), asthenia (13%) and nausea, diarrhea and anorexia (1% each). On an intent to treat basis, the R0 resection rate was 55% (38/69). Among resected patients, local and distant failure rates were 5 and 55% respectively. After a median follow up of 43 months (range 9 to 88), median PFS was 17, 9 and 1 month in groups A, B and C respectively. Median overall-survival (mOS) was 13 and 4 months in groups B and C. In group A mOS has not been reached. The 2 and 3-year actuarial overall survival in this group are 71% and 45% respectively. Conclusions Our data suggest that this three-step strategy is feasible and active in LAPC patients Correlative molecular analysis seem warranted to rule out the subset of pts most likely to benefit from this approach. Disclosure All authors have declared no conflicts of interest.

Treatment outcomes of definitive chemoradiotherapy for patients with hypopharyngeal cancer

We analyzed the efficacy of definitive chemoradiotherapy (CRT) for patients with hypopharyngeal cancer (HPC). Subjects comprised 97 patients who were treated with definitive CRT from 1990 to 2006. Sixty-one patients (62.9%) with resectable disease who aimed to preserve the larynx received induction chemotherapy (ICT), whereas 36 patients (37.1%) with resectable disease who refused an operation or who had unresectable disease received primary alternating CRT or concurrent CRT (non-ICT). The median dose to the primary lesion was 66 Gy. The median follow-up time was 77 months. The 5-year rates of overall survival (OS), progression-free survival (PFS), local control (LC), and laryngeal preservation were 68.7%, 57.5%, 79.1%, and 70.3%, respectively. The T-stage was a significant prognostic factor in terms of OS, PFS and LC in both univariate and multivariate analyses. The 5-year rates of PFS were 45.4% for the ICT group and 81.9% for the non-ICT group. The difference between these groups was significant with univariate analysis (P = 0.006). Acute toxicity of Grade 3 to 4 was observed in 34 patients (35.1%). Grade 3 dysphagia occurred in 20 patients (20.6%). Twenty-nine (29.8%) of 44 patients with second primary cancer had esophageal cancer. Seventeen of 29 patients had manageable superficial esophageal cancer. The clinical efficacy of definitive CRT for HPC is thought to be promising in terms of not only organ preservation but also disease control. Second primary cancer may have a clinical impact on the outcome for HPC patients, and special care should be taken when screening at follow-up.

Induction chemotherapy versus palliative treatment for acute myeloid leukemia in a consecutive cohort of elderly patients

A retrospective survey of 210 consecutive patients aged ≥ 65 years (median age 69 years, range 65-88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p = 0.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p = 0.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p = 0.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p = 0.000, CI 95 % 2.209-3.458), absence of splenomegaly (p = 0.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p = 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p = 0.000), the ECOG PS (p = 0.045) and the ECOG PS (p = 0.000), and HCT-CI (p = 0.000) in the NIC group of elderly patients. The present study suggests that a subgroup of elderly patients with both ECOG PS and HCT-CI ≤ 2 at presentation may be eligible for intensive induction chemotherapy.

Clinical relevance of induction triplet chemotherapy for esophageal cancer invading adjacent organs

There is no consensus on treatment for esophageal cancer invading adjacent organs (T4), but induction multidrug chemotherapy may be a beneficial, especially when surgery is considered as adjuvant treatment. We classified 169 patients with T4 esophageal cancer without distant metastasis into those undergoing chemotherapy using cisplatin and 5-FU (CF) plus adriamycin or CF plus docetaxel (79 patients) and those undergoing chemoradiotherapy using CF (90 patients). For the former group, chemoradiation was subsequently applied when surgical resection was not indicated. Thirty-four patients in the chemotherapy group (43.0%) received chemoradiotherapy following chemotherapy. Although the response rate tended to be higher in the chemoradiotherapy group, there was no significant difference in the response rate between the groups (63.3% vs. 68.9%). Esophageal perforation during treatment was more frequent among the chemoradiotherapy group than the chemotherapy group (16.7% vs. 6.3%, P=0.0379). The rate of surgical resection was consequently higher for the induction chemotherapy group compared to the chemoradiotherapy group (72.1% vs. 45.6%, P=0.0005). Induction triplet chemotherapy reduced esophageal perforation and increased the resectability of T4 esophageal cancers by combining second-line chemoradiotherapy. This strategy might increase the chance of curative resection for patients with T4 esophageal cancer.

Pretransplantation Therapy with Azacitidine vs Induction Chemotherapy and Posttransplantation Outcome in Patients with MDS

Although allogeneic hematopoietic cell transplantation (HCT) has proven curative potential for myelodysplastic syndrome, relapse after HCT remains a problem. Pretransplantation cytoreduction with induction chemotherapy (IC) has been used to reduce relapse rates but is associated with significant toxicity and mortality. Hypomethylating agents may achieve cytoreduction with limited toxicity; however, data on the effect of pre-HCT hypomethylation on post-HCT outcomes are limited. We retrospectively reviewed results in 68 patients who underwent allogeneic HCT for myelodysplastic syndrome or acute myeloid leukemia transformed from MDS. Thirty-five patients had received cytoreduction with azacitidine before HCT with either a high-dose (40%) or a reduced-intensity (60%) conditioning regimen, and 33 had undergone IC before HCT with high-dose conditioning. The estimated 1-year overall survival (OS) was 57% in the azacitidine group and 36% in the IC group. The risk of post-HCT mortality (hazard ratio, 0.68; 95% confidence interval, 0.35-1.30), nonrelapse mortality (hazard ratio, 0.99; 95% confidence interval, 0.41-2.34), and relapse (hazard ratio, 0.34; 95% confidence interval, 0.41-2.34) were lower in the azacitidine group compared to the IC group, but only the hazard for relapse was significantly lower. After adjustment for cytogenetic risk, International Prognostic Scoring System, and donor, the rates of post-HCT relapse for the 2 cohorts were similar. Although the current study was retrospective and nonrandomized and needs to be interpreted in this context, the results add to the growing evidence that pre-HCT therapy with azacitidine is associated with less toxicity than IC and may allow for similar post-HCT outcomes.

The Feasibility of (18)F-Fluorothymidine PET for Prediction of Tumor Response after Induction Chemotherapy Followed by Chemoradiotherapy with S-1/Oxaliplatin in Patients with Resectable Esophageal Cancer.

The aim of this study was to determine whether (18)F-fluorothymidine (FLT) PET is feasible for the early prediction of tumor response to induction chemotherapy followed by concurrent chemoradiotherapy in patients with esophageal cancer. This study was prospectively performed as a collateral study of "randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1/oxaliplatin in patients with resectable esophageal cancer". (18)F-FLT positron emission tomography (PET) images were obtained before and after two cycles of induction chemotherapy, and the percent change of maximum standardized uptake value (SUVmax) was calculated. All patients underwent esophagography, gastrofiberoscopy, endoscopic ultrasonography (EUS), computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) PET at baseline and 3-4weeks after completion of concurrent chemoradiotherapy. Final tumor response was determined by both clinical and pathologic tumor responses after surgery. The 13 patients for induction chemotherapy group were enrolled until interim analysis. In a primary tumor visual analysis, the tumor detection rates of baseline (18)F-FLT and (18)F-FDG PET were 85% and 100%, respectively. The tumor uptakes on (18)F-FLT PET were lower than those of (18)F-FDG PET. Among nine patients who completed second (18)F-FLT PET, eight patients were responders and one patient was a non-responder in the assessment of final tumor response. The percent change of SUVmax in responders ranged from 41.2% to 79.2% (median 57.1%), whereas it was 10.2% in one non-responder. The percent change of tumor uptake in (18)F-FLT PET after induction chemotherapy might be feasible for early prediction of tumor response after induction chemotherapy and concurrent chemoradiotherapy in patients with esophageal cancer.

Impact of chemotherapy compliance on the therapeutic efficacy of patients with locally advanced nasopharyngeal carcinoma

Objective To evaluate the impact of chemotherapy compliance on the therapeutic efficacy of induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus radiotherapy alone for patients with locally advanced nasopharyngeal carcinoma （ NPC ）. Methods Based on intention to treat analysis （ITT） for 400 patients, 314 patients were analyzed by per protocol （PP） analysis. The patients were divided into induction chemotherapy plus concurrent chemoradiotherapy group （IC/CCRT, 127 patients） or induction chemotherapy plus radiotherapy group （IC/RT, 187 patients）. The patients who completed 2 cycles of induction chemotherapy and at least 2 cycles of concurrent chemotherapy in the IC/CCRT group and the patients who completed 2 cycles of induction chemotherapy in the IC/RT group were analyzed. Radiotherapy was given by two-dimensional technique with γ-ray. X-ray and electron beams. The chemotherapy regimen was FUDR plus carboplatin for induction chemotherapy and carboplatin alone for concurrent chemotherapy. Results The follow-up rate was 96.2%. 295 patients were followed to at 3 years. Based on PP analysis, Grade 3/4 toxicity was found in 23.6% of the patients in IC/CCRT group and 13.4% in the IC/RT group （χ^2 = 5.50, P = 0. 019）. No grade 4 toxicity was found in the IC/RT group. The median follow-up time was 3.9 years, and no significant difference was found between the two groups in 3-year overall survival （78.1% ： 84.6% ;χ^2 =0.61 ,P =0. 435） , disease-free survival （74.3% ： 70. 1% ; χ^2 = 0. 12, P= 0.731 ）, locoregional relapse-free survival （89.7% ： 89.5% ; χ^2 = 0. 10, P= 0.748） , or distant metastasis-free survival （78.9%： 76.5% ;χ^2 =0.05,P=0.825）. Condusions With more severe toxicities, the IC/CCRT regimen does not improve the overall survival in locally advanced NPC patients compared with the IC/RT regimen. Key words: Nasopharyngeal neoplasms/chemoradiotherapy ; Radiotherapy, two-dimensional ; Chemotherapy,induction ; Chemotherapy,concurrent ; Prognosis

Randomized phase III trial comparing induction chemotherapy followed by radiotherapy to concomitant chemoradiotherapy for laryngeal preservation in T3M0 pyriform sinus carcinoma

Conclusions. Conventional radiotherapy with concurrent cisplatin is significantly superior to induction cisplatin fluorouracil chemotherapy followed by radiotherapy in terms of laryngeal preservation in patients with T3 hypopharyngeal carcinoma. Despite a high rate of laryngeal preservation no survival benefit was recorded in this selected population. Objectives. To compare conventional radiotherapy with concurrent cisplatin to induction chemotherapy with cisplatin fluorouracil followed by conventional radiotherapy. The primary end point was the preservation of the larynx. The secondary end points included toxicity, causes of death, and survival rates. Patients and methods. Seventy-one adult patients with previously untreated resectable T3 pyriform sinus squamous cell carcinoma were enrolled in the multicenter prospective randomized phase III trial. They were evaluated for organ preservation, survival rates, and toxic reactions. Results. The rates of laryngeal preservation at 2 years were 68% for the induction chemotherapy (IC) group and 92% for the chemoradiotherapy (CR) group (p = 0.016). At 2 years, the event-free survival rates were 36% and 41% for the IC group and CR group, respectively.

Predictors of survival in patients with locally advanced thymoma and thymic carcinoma (Masaoka stages III and IVa)☆

We sought to evaluate factors influencing long-term survival of patients with locally advanced thymoma/thymic carcinoma (Masaoka stages III and IVa) treated by immediate surgery or induction therapy plus surgery. From January 1991 to April 2007, we surgically treated 61 patients with locally advanced thymoma/thymic carcinoma (Masaoka stages III and IVa). Staging included total body computed tomography (CT) scan in all patients, and chest magnetic resonance imaging (MRI) in 27 selected patients. All patients had histological confirmation before surgery. Thirty-one patients (group A) underwent induction chemotherapy followed by surgery. Thirty patients (group B) underwent immediate surgery. Thirty-four patients (group A: 13; group B: 17) received postoperative radiation therapy. No intra-operative mortality was reported. World Health Organization (WHO) histological classification included 19 AB, four B1, seven B2 and 13 B3 thymomas and 18 thymic carcinomas. Thirty-four patients were Masaoka stage III (group A: 18; group B: 16) and 27 patients were stage IVa (group A: 13; group B: 14). After a median follow-up of 77 months, six patients of group A and seven patients of group B died of disease. The overall 10-year survival rate was 50.6%. The 10-year survival rate was 57.9% in group A and 38.1% in group B (p=0.03). Multivariate analysis showed complete resection (p=0.02), Masaoka stage (III vs IVa) (p=0.02), induction chemotherapy (group A vs group B) (p=0.003) and histological WHO subtype (AB vs B1, B2 and B3) (p=0.01) to be statistically significant independent predictors of survival. Sex, age and adjuvant radiation therapy showed no statistically significant difference. Complete resection, Masaoka stage, induction chemotherapy and histological WHO classification showed to be independent predictors of survival in locally advanced thymoma/thymic carcinoma.

Induction Chemotherapy Before Sleeve Lobectomy for Lung Cancer: Immediate and Long-Term Results

Induction chemotherapy does not increase the morbidity and mortality rates of bronchoplastic procedures, but the long-term efficiency remains unclear. The purpose of this retrospective study was to analyze the impact of chemotherapy on resectability and long-term survival. From 1984 to 2005, 159 consecutive patients with non-small cell lung cancer underwent sleeve lobectomy without (n = 117) or with induction chemotherapy (n = 42). Indications for chemotherapy were N2 lymph node involvement (n = 15), T3 or T4 tumor invasion with doubtful resectability (n = 13), need for tumor size reduction (n = 8), lung function precluding pneumonectomy (n = 4), and brain metastasis (n = 2). None of the patients received induction radiation therapy. We studied tumor characteristics and immediate and long-term results in both groups. Clinical stage III was predominant in the induction chemotherapy group whereas stage II was predominant in the surgery-only group. Complication rates in the induction chemotherapy group and in the surgery-only group were 23.8% and 24.7%, respectively. We observed a greater rate of 1-month-delay smoking cessation before surgery in the induction chemotherapy group (40% versus 22%). The 5-year survival rates were 65.4% in the surgery-only group and 73.4% in the induction chemotherapy group (p = 0.5). The tumor size in the induction chemotherapy group was lower (17.5 versus 30.6 mm; p = 0.01), which reflected the positive impact of chemotherapy on sleeve resection feasibility. Induction chemotherapy before sleeve lobectomy achieves good long-term results. Tumor reduction and limited resection feasibility seemed to be increased, which justify further prospective trials.