Role Of Induction Chemotherapy Research Articles

The role of induction chemotherapy in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck

The role of induction chemotherapy in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck

Comparison of Functional Larynx Preservation in Patients with Locally Advanced Squamous Cell Carcinoma of the Larynx and Hypopharynx Treated with Induction Chemotherapy vs Concurrent Chemoradiation Alone

Functional organ preservation is an important outcome measure in the treatment of squamous cell carcinoma (SCC) of the larynx and hypopharynx (HPX) as laryngectomy is associated with significant morbidity. Numerous studies have established the efficacy of larynx preservation with concurrent chemoradiation therapy (CRT) in the setting of locally advanced disease. However, the role of induction chemotherapy (IC) remains a topic of ongoing investigation. This study aims to compare outcomes of patients with locally advanced SCC of the larynx and HPX who received either IC plus CRT to those who received CRT alone. The primary outcome is to determine whether the addition of IC improves functional larynx-preservation survival (FLPS) in patients treated with definitive CRT for stage III-IV SCC of the larynx and HPX. Secondary outcomes are laryngectomy rate, overall survival (OS), and progression-free survival (PFS). Records of patients with clinical stage III and IV SCC of the larynx and HPX treated non-operatively between 2005 and 2019 were identified. Eligible patients were at least 18 years of age, had pathologically confirmed SCC of the larynx or HPX, and were treated definitively with IC plus CRT or CRT alone. Patients with distant metastases were excluded. FLPS was defined as the time until death, local progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, and PFS. These outcomes were compared using the stratified log-rank test and laryngectomy rates were compared using Fisher’s Exact Test, where a p-value < 0.05 was considered statistically significant. Ninety patients met inclusion criteria: 52 patients had laryngeal SCC; 19 received IC plus CRT and 33 were treated with CRT alone. Thirty-eight patients had SCC of the HPX; 19 received IC plus CRT and 19 were treated with CRT alone. The median follow-up was 24 months. There were no significant differences in T stage between the IC and CRT arms. Patients who underwent IC received a median of 3 cycles (range 1-6). There was no difference in 3-year FLPS (61% vs 67.8%; p = 0.88), OS (73.9% vs 86.2%; p = 0.42) or PFS (53.6% vs 62.6%; p = 0.44) between the IC plus CRT vs CRT, respectively, in the entire cohort. These outcomes were also not statistically different between the two groups when stratified by primary site of larynx or HPX. Laryngectomy rates were not statistically different between those receiving IC compared to CRT alone (18.4 % vs 7.7%; p = 0.19). This result was also seen on subset analysis by site. In this retrospective study of patients with locally advanced SCC of the larynx and HPX, IC did not significantly improve 3-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone for the entire cohort or on subgroup analysis by site. A large prospective series would provide a more robust understanding of the role of IC in this group of patients.

Meta-Analysis on Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma.

PurposeConcurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA‐NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta‐analysis investigates the value of adding ICT to CCRT in LA‐NPC.Materials and MethodsTwo reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment‐naive adult patients with histologically proven nonmetastatic LA‐NPC.ResultsEight RCTs with in total 2,384 randomized patients, of whom 69% had N2–N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%–100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) –0.001–0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, −0.243; 95% CI, −0.403 to −0.083; p = .003). Grade 3–4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511–0.905; p = .001) and progression‐free survival (HR, 0.657; 95% CI, 0.568–0.760; p < .001).ConclusionAlthough ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA‐NPC, but further study on optimal patient selection for this treatment is warranted.Implications for PracticeLocally advanced nasopharyngeal carcinoma (LA‐NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta‐analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA‐NPC is associated with a significant clinical improvement in both overall survival and progression‐free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA‐NPC.

Induction chemotherapy in nonlaryngeal human papilloma virus-negative high-risk head and neck cancer: a real-world experience.

The role of induction chemotherapy in the multidisciplinary treatment of locally advanced, nonlaryngeal high-risk human papilloma virus (HPV)-negative head and neck squamous cells carcinoma (HNSCC) is uncertain in terms of overall survival (OS). The primary objective of this study was to identify possible predictive factors of survival and outcome in patients with HNSCC who were treated with induction chemotherapy. Fifty-nine patients with stage IVa/b HPV-negative non-laryngeal HNSCC (mostly originating from the oral cavity) who underwent induction chemotherapy at Policlinico Umberto I were reviewed. Treatment outcomes in term of objective response rate (ORR), progression-free survival (PFS), OS and toxicities were analyzed. A significant association between nodal status, ORR, ongoing smoking use, toxicities and OS was demonstrated. ORR (obtained in 61% of patients) was associated with a reduction in mortality of 80% (P< 0.0001). Early discontinuation after just one cycle of induction chemotherapy was associated to a significantly shorter OS. In oral cavity radical surgery with negative margins was obtained in 15/16 patients. In 42% of patients G3-G4 toxicity occurred. Toxicity requiring hospitalization occurred in 42% and 21% of patients with oropharyngeal and oral cavity carcinoma, respectively. Five patients died of treatment-related causes. No treatment-related mortality occurred in oral cavity patients. G5 toxicities were different according to the sub-sites of disease (P = 0.05). Induction chemotherapy in non-laryngeal high-risk HNSCC is an active strategy, most importantly in oral cavity cancer, even though burdened with a high (G ≥ 3) toxicity and early discontinuation rate. These data will however need to be confirmed in further and larger studies.

Induction chemotherapy followed by radiotherapy for N3 head and neck squamous cell carcinoma.

The treatment outcomes for N3 HNSCC treated with induction chemotherapy (ICT) followed by definitive radiation were reported to clarify the role of ICT and potential prognostic factors. A retrospective study was conducted on 120 patients with N3 (≥6 cm) HNSCC, who were treated with ICT as initial treatment. Survival outcomes and potential prognostic factors were reported. The response rate to ICT was 68.3%. There was a statistically significant difference between responders and non-responders in terms of 5-year OS (35.1% vs 13.3%, P < .001) and PFS (29.4% vs 7.4%, P < .001). Good response to ICT (P < .001) and upfront neck dissection (UFND) before radiotherapy (P = .016) were factors predicting for better OS. However, UFND before radiotherapy was not associated with improved outcomes among responders. This study suggests that ICT could be one treatment option for N3 HNSCC. Among responders to ICT, UFND before radiotherapy could be avoided.

Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma

The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach. PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019. Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC. Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC. These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

Induction Chemotherapy for Locally Advanced Esophageal Cancer.

Concurrent chemoradiotherapy followed by surgery is the standard treatment for locally advanced esophageal cancer (EC), and the role of induction chemotherapy (IC) remains unclear. We aimed to study if the addition of IC to standard treatment increases the rate of pathologic complete response (pCR). We assembled a retrospective analysis of patients (pts) diagnosed with locally advanced EC and treated with preoperative chemoradiotherapy followed by esophagectomy (CRT+S), preceded or not by IC, between 2009 and 2017. Patients' characteristics, tumor variables, and treatment outcomes were evaluated. The Kaplan-Meier method was used to estimate overall survival and the Cox proportional hazard model to evaluate prognostic factors. One hundred and three patients were studied, with a median age of 62years (range 37-84). Seventy-five patients (73%) were male, 67 (65%) had squamous cell carcinoma, and 31 (30%) had adenocarcinoma. Forty-three patients (41.7%) received IC followed by CRT+S (IC+CRT+S). The most frequent IC consisted of paclitaxel and platinum chemotherapy (90%), and the median number of cycles was 2. All patients received CRT+S. Concurrent chemotherapy was a combination of paclitaxel and platinum in 94 patients (91%). There was no statistically significant difference in pCR between the IC group and the standard CRT+S group. The pCR was 41.9% and 46.7% in the IC+CRT+S and CRT+S groups (p = 0.628), respectively. In the multivariate analysis, pCR was an independent prognostic factor for time to treatment failure (TTF) (HR 0.35, p = 0.021), but not for overall survival (OS) (p = 0.863). The factor that significantly affected OS in the multivariate analysis was positive lymph node (HR 5.9, 95%, p = 0.026). Our data suggest that the addition of IC to standard CRT + S does not increase the pCR rate in locally advanced EC. No difference in OS was observed between pts. that received or not IC. Regardless of the treatment received, pts. achieving a pCR presented improved TTF.

Induction chemotherapy with docetaxel, cisplatin and cetuximab versus docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy with cetuximab for locally advanced or inoperable squamous cell carcinoma of the head and neck: Promising results of a randomized phase II AGMT-trial.

6027 Background: Induction chemotherapy (ICT) with Cisplatin (P), 5-FU (F) and Taxanes (T) is a therapeutical option in patients suffering from locally advanced or unresectable stage III or IV squamous cell carcinoma of the head and neck (SCCHN). The role of ICT is controversial and toxicity and/or delay of radiotherapy may reduce the potential benefit of this treatment regimen. Here we report promising results of a randomized phase II trial comparing TPF with TP and Cetuximab (C) replacing F. Methods: In our trial, N= 100 patients with locally advanced or unresectable stage III or IV SCCHN were randomly assigned to either Arm A ( N= 49), receiving TPF, or Arm B ( N= 51), receiving TPC, both followed by radiotherapy (RT) + C. The primary end-point of the study was overall response rate (ORR) three months after RT + C was finished. Results: We observed a remarkable response rate (CR + PR) of 86.4% in the TPC-arm that compared favorably with 77.5% responding patients in the TPF-arm three months after RT + C was completed. OS and PFS were similar in both arms. After 400 days we observed an OS rate of 79% in the TPF and 86% in the TPC arm, and a PFS rate of 67% in the TPF and 70% in the TPC arm. TPC containing ICT led to less serious adverse events (SAEs), including blood and lymphatic disorders (40.8% in TPF arm, 27.5% in TPC arm) and metabolism and nutrition disorders (22.4% in TPF arm, 9.8% in TPC arm) during ICT. Interestingly, in HPVp16 positive patients, 88.24% in the TPF-arm and 93.33% in the TPC-arm showed CR or PR three months after RT + C, whereas only 69.57% in the TPF-arm and 82.76% in the TPC-arm showed CR or PR. We only lost one patient because of treatment-related mortality (TRM) and no delay from the end of ICT to local radiotherapy was observed in any patient. All patients received RT + C within three weeks after ICT was completed. Conclusions: In conclusion, TPC is a feasible and tolerable therapy regimen and can be applied within one day with less hematological toxicities. In contrast, more local reactions were observed after TPC. TPC containing ICT leads to improved response rates, while OS and PFS were similar in both arms. TRM was extremely low with 1%. Therefore, we conclude, that TPC containing ICT could be a considerable therapeutical alternative for patients with locally advanced or unresectable stage III or IV SCCHN, who are eligible for ICT. Clinical trial information: 2011-005540-99.

Therapeutic Intensification and Induction Chemotherapy for High-Risk Locally Advanced Squamous Cell Carcinoma.

The treatment of HNSCC has rapidly evolved over the past 30years and multidisciplinary management is required, especially for locally advanced disease (LAHNSCC). Concomitant chemoradiation (cCRT) is the standard of care and cetuximab/RT (CET/RT) is an alternative treatment option, especially for patients unfit for concurrent cisplatin. Several intensification strategies have been explored to improve the outcome of the concomitant treatment. The combination of cisplatin plus cetuximab concurrent to RT failed to improve overall survival (OS) in two phase III trials. Induction chemotherapy (IC) has a proven role in organ preservation; however, its ability in prolonging OS has not been clearly demonstrated. Immune checkpoint inhibitors (ICIs), specifically anti PD-1 inhibitors, have been recently approved for the treatment of patients with recurrent/metastatic platinum-refractory disease. Recent clinical trials are exploring the role of immunotherapy at earlier stages of the disease in combination with concomitant treatments. The purpose of this article is to review current evidence regarding treatment intensification strategies for LAHNSCC (except nasopharyngeal carcinomas) with particular emphasis on the role of induction chemotherapy.

Impact of Induction Chemotherapy on Nodal and Distal Disease Control in Locally Advanced Buccal Mucosa Cancer

Background: Buccal mucosa squamous cell cancer is the most common cancer in India. Majority of them presenting in advanced stage whose prognosis after surgery depends significantly upon the regional and distal spread. We studied the impact of neoadjuvant chemotherapy (NACT) on nodal and distal control of disease in operated cases of advanced buccal mucosa cancer. Aim: A retrospective study to evaluate the impact of induction chemotherapy (NACT) on nodal and distal failure in locally advanced buccal mucosa cancer. Methods: A total of 224 patients of advanced buccal mucosal cancer who underwent surgery between 2014 and 2015 were evaluated retrospectively with a follow-up of two years. Total 111 of the above had received NACT prior to surgery while 113 patients underwent upfront surgery. The CT scans and histologic reports were then compared for evaluation and analysis. Results: Among patients with T4a disease, 45.85% in upfront surgery group compared with 54% in NACT group showed metastatic pathologic nodes, while in T4b patients, the rates were 83.33% compared with 49.18% respectively. In patients with clinical/radiologic positive neck nodes at presentation, 87.5% in upfront surgery group as compared with 55.55% in NACT group showed metastatic nodes in histopathologic evaluation. 13.27% patients in the upfront surgery group had nodal and/or distal failure in the two years follow-up, whereas only 3.6% patients in the NACT group. 25% patients with peri-nodal extension in upfront surgery group showed nodal and/or distal failure, while only 6% in NACT group. The results in different nodal-ratio strata was evaluated. It showed that NACT has equal failure rate as in upfront group in nodal-ratio &gt; 50, which is considered as very advanced and aggressive tumor. But in patients with nodal-ratio &lt; 50, NACT group showed lesser failure rate than upfront group. Conclusion: We show regressional effect of NACT on nodal metastases. This study also shows NACT to be having a significantly positive impact on nodal and distal control. Hence role of induction chemotherapy needs to be considered in advanced cases of buccal mucosa cancer with nodal metastases.

Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care.

The role of induction chemotherapy in nasopharyngeal carcinoma (NPC) remains controversial. The primary aim of this study was to use the National Cancer Database to evaluate the patterns of care of induction chemotherapy in NPC and its impact on overall survival (OS). Patients with NPC from 2004 to 2014 were obtained from the NCDB. Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT and concurrent CRT if chemotherapy started within 21 days after the start of RT. Propensity score matching was used to control for selection bias. Cox proportional hazards model was used to determine significant predictors of OS. Logistic regression model was used to determine predictors of the use of induction chemotherapy. Significance was defined as a P value <.05. A total of 4857 patients were identified: 4041 patients (87.2%) received concurrent CRT and 816 patients (16.8%) received induction chemotherapy. The use of induction therapy remained stable between 2004 and 2014. Younger patients and those with higher T‐ and N‐stage had a higher likelihood of being treated with induction chemotherapy. The 5‐year OS in patients treated with induction chemotherapy and CRT was 66.3% vs 69.1%, respectively (P = .25). There was no difference in OS when these two groups were analyzed after propensity score matching. No differences in OS existed between these treatment groups in patients with T3‐T4N1 or TanyN2‐3 disease (P = .76). Propensity score matching also did not reveal any difference in OS in patients with T3‐T4N1 or TanyN2‐3 disease. The use of induction chemotherapy has remained stable in the last decade. In this study of patients with NPC, induction chemotherapy was not associated with improved OS compared to CRT alone.

A randomized trial of induction docetaxel–cisplatin–5FU followed by concomitant cisplatin-RT versus concomitant cisplatin-RT in nasopharyngeal carcinoma (GORTEC 2006-02)

BackgroundConcomitant chemotherapy (CT)–radiotherapy (RT) is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established. MethodsPatients with locally advanced NPC, WHO type 2 or 3, were randomized to induction TPF plus concomitant cisplatin-RT or concomitant cisplatin-RT alone. The TPF regimen consisted of three cycles of Docetaxel 75mg/m2 day 1; cisplatin 75mg/m2 day 1; 5FU 750mg/m2/day days 1–5. RT consisted of 70Gy in 7weeks plus concomitant cisplatin 40mg/m2 weekly. ResultsA total of 83 patients were included in the study. Demographics and tumour characteristics were well balanced between both arms. Most of the patients (95%) in the TPF arm received three cycles of induction CT. The rate of grade 3–4 toxicity and the compliance (NCI-CTCAE v3) during cisplatin-RT were not different between both arms. With a median follow-up of 43.1months, the 3-year PFS rate was 73.9% in the TPF arm versus 57.2% in the reference arm [hazard ratio (HR)=0.44; 95% confidence interval (CI): 0.20–0.97, P=0.042]. Similarly the 3years overall survival rate was 86.3% in the TPF arm versus 68.9% in the reference arm (HR=0.40; 95% CI: 0.15–1.04, P=0.05). ConclusionIn conclusion, several important aspects can be emphasized: the compliance to induction TPF was good and TPF did not compromise the tolerance of the concomitant RT-cisplatin phase. The improved PFS and overall survival rates needs to be confirmed by further trials.

Induction chemotherapy followed by concurrent chemoradiation versus concurrent chemoradiation alone in the definitive management of p16-positive oropharyngeal squamous cell carcinoma with low-neck or N3 disease

ObjectiveThe addition of induction chemotherapy (ICT) to concurrent chemoradiation (CCRT) has been investigated as a method of improving outcomes among patients with locally advanced head and neck squamous cell carcinoma. Previous studies have consisted of heterogeneous populations with both p16-positive and p16-negative disease and varying extent of nodal disease burden. We evaluated the role of ICT in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) at high-risk of distant failure. Materials and methodsA retrospective review was conducted of 88 consecutive patients with p16-positive OPSCC with low-neck and/or N3 lymphadenopathy. Among these patients, 44 received ICT followed by CCRT, and 44 received CCRT alone with concurrent agents including Cisplatin, Carboplatin, and Cetuximab. Disease control and survival outcomes were reported after adjusting for age, T stage, N stage, and smoking status. ResultsMedian follow-up for surviving patients was 47 (range: 13–115) months. Patients who received CCRT alone were older than those who received ICT (61 years vs. 56 years; p = 0.02); the groups were otherwise similarly balanced. 3-year distant metastasis: 38% vs. 18% (adjusted hazard ratio (HR) = 0.32 [0.13–0.82]; p = 0.02). 3-year progression-free survival: 49% vs. 74% (adjusted HR = 0.46 [0.22–0.93]; p = 0.03). 3-year overall survival: 67% vs. 83% (adjusted HR = 0.48 [0.21–1.12]; p = 0.09). ConclusionAmong patients with p16-positive OPSCC with low-neck and/or N3 lymphadenopathy, ICT followed by CCRT may reduce the risk for distant failure over CCRT alone and lead to improved progression-free survival. Future trials should concentrate on patients at the highest risk of distant metastasis in order to appropriately assess the benefit of ICT.

Role of Induction Chemotherapy in Orbital Preservation in the Management of Advanced-Stage Sinonasal Malignancies: A Systematic Review

Role of Induction Chemotherapy in Orbital Preservation in the Management of Advanced-Stage Sinonasal Malignancies: A Systematic Review

The role of induction chemotherapy followed by surgery in unresectable stage IVb laryngeal and hypopharyngeal cancers: a case series

BackgroundThe purpose of this study was to evaluate the benefit of induction chemotherapy followed by surgery in locally advanced unresectable stage IVb laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC).MethodsData of patients with stage IVb LHSCC who received induction chemotherapy for the purpose of tumor resection between January 2007 and January 2016 were retrospectively collected. Definitive surgery with postoperative adjuvant therapy was performed in patients whose tumors became resectable (resectable group). Chemoradiotherapy, radiotherapy, or supportive care was considered in patients whose tumors remained unresectable (unresectable group).ResultsThirty-two patients were identified; the tumor resectability rate after induction chemotherapy was approximately 56%. The median overall survival (OS) rates of the resectable and unresectable groups were 20.0 months (range, 16.0–35.5 months) and 9.5 months (range, 6.0–15.0 months), respectively (p = 0.008). The estimated 2-year OS rates of the resectable and unresectable groups were 59.5% (95% confidence interval [CI], 33.2–78.3%) and 10.7% (95% CI, 1.1–35.4%), respectively (p = 0.008). The estimated 2-year disease-free survival (DFS) rates of the resectable and unresectable groups were 53.5% (95% CI, 27.9–73.6%), and 14.3% (95% CI, 2.3–36.6%), respectively (p = 0.009). On multivariate analysis, factors positively impacting OS and DFS in all patients were surgical resection, a laryngeal primary site, and induction chemotherapy with docetaxel, cisplatin, and fluorouracil.ConclusionsIn advanced unresectable stage IVb LHSCC patients, surgical resection following induction chemotherapy appears to improve survival outcomes.

Role of induction chemotherapy in downstaging of locally advanced head-and-neck squamous cell cancer

Aims and Objectives: To study the effect of induction chemotherapy (CT) in locally advanced head-and-neck squamous cell carcinoma (LAHNSCC) and to compare the two commonly used regimens of CT, including paclitaxel and cisplatin (CDDP) in one arm and CDDP, methotrexate (MTX), and bleomycin in the other arm as induction CT. Materials and Methods: It is a retrospective study, including 100 histopathologically proven cases of LAHNSCC who received treatment at a government medical college and hospital in Central India between November 2015 and June 2016. All the patients were randomly divided into two arms: arm A received paclitaxel + cisplatin (TP) and arm B received cisplatin + MTX + bleomycin as induction CT had adequate hematologic, hepatic, and renal functions, and their response to treatment was evaluated clinically after each cycle up to three cycles before external beam radiotherapy. Results: The present study showed beneficial effects of induction CT in HNSCC as 82% of the patients showed response or T-downstaging. Among the patients responding to induction CT, 34% showed complete and 48% showed partial response at the primary tumor site according to Response Evaluation Criteria in Solid Tumors. The difference in response between the two arms was statistically significant (P = 0.037). Conclusion: The current study shows the beneficial effects of induction CT in LAHNSCC. No statistically significant difference was seen in the response of both regimens of induction CT in terms of overall survival, but significant disease-free survival and progression-free survival were obtained in the TP arm.

Induction Chemotherapy Followed by Concurrent Chemoradiation versus Concurrent Chemoradiation Alone in the Definitive Management of p16-positive Oropharyngeal Cancer with Low-neck or N3 Disease

The role of induction chemotherapy (ICT) in addition to concurrent chemoradiation (CCRT) in the definitive management of locally advanced oropharyngeal cancer is controversial. At our institution, certain patients with low-neck (level IV and/or Vb) or N3 lymphadenopathy are given ICT prior to CCRT at the discretion of the treating physicians with the objective of lowering the risk of distant failure. We compared the outcomes of these patients to their counterparts who received upfront CCRT alone. A retrospective review was conducted from June 2006 through June 2015. Out of 548 patients with locally advanced p16-positive oropharyngeal cancer, 88 were identified with low-neck and/or N3 disease. Among these patients, 44 received upfront CCRT, and 44 received ICT followed by CCRT. Upfront CCRT regimens included triweekly Cisplatin (43%), triweekly Carboplatin (32%), Cetuximab (14%), and weekly Cisplatin (11%). ICT regimens were Docetaxel and platinum based chemotherapy with (89%) or without 5-fluorouracil (11%) followed by CCRT using weekly Carboplatin (61%), triweekly Carboplatin (18%), weekly Cisplatin (11%), triweekly Cisplatin (7%), or Cetuximab (2%). All patients were planned for 70 Gy with intensity-modulated radiotherapy. Pathology review was performed of all cases with standardized p16 reporting. Median follow-up for surviving patients was 45 [13-115] months. Median age was lower in the ICT group compared to the CCRT group, 56 vs. 61, respectively (P = 0.02), with T stage, N stage, and rates of low-neck disease similar between the two groups. Compared to CCRT alone, ICT followed by CCRT was associated with a significant improvement in the rate of distant metastases (DM) (3-year: 18% vs. 37%; P = 0.01), progression-free survival (PFS) (3-year: 74% vs. 49%; P = 0.008), and overall survival (OS) (3-year: 82% vs. 67%; P = 0.05). No difference in locoregional failure was observed (3-year: 14% for both arms). Patients in the upfront CCRT group were more likely to require a feeding tube compared to the ICT group (27% vs. 57%; P = 0.005). Among ICT patients, 75% received 3 cycles of ICT with the remaining 25% receiving only 2 cycles either due to treatment-related toxicities, performance status, or suboptimal response to ICT. In this cohort of p16-positive oropharyngeal cancer patients with low-neck and/or N3 disease at high risk of distant failure, ICT followed by CCRT demonstrated a statistically significant reduction in DM which translated into an improvement in PFS and OS over upfront CCRT alone. Future randomized studies should concentrate on patients at the highest risk of developing distant metastases in order to assess the potential benefit of ICT in addition to CCRT in this population. Less intensive CCRT regimens employed in patients receiving ICT may have led to decreased rates of feeding tube placements compared to that observed in CCRT alone patients.

1075P - Role of induction chemotherapy in locally advanced T4b oral cavity cancers: A single Institute experience

1075P - Role of induction chemotherapy in locally advanced T4b oral cavity cancers: A single Institute experience

The role of induction chemotherapy + chemoradiotherapy in localised pancreatic cancer: initial experience in Scotland.

Despite being relatively rare pancreatic cancer is one of the highest causes of death. Even within the potentially resectable group outcomes are poor. We present our initial experiences utilising a neoadjuvant approach to localised pancreatic cancer, evaluating survival, response rates and tolerability. This was a retrospective analysis of a prospectively maintained database. Patients from 2012 to 2015 referred to a busy regional Hepato-Pancreatic Biliary (HPB) MDT were included. Patients were classified according to respectability criteria (utilising NCCN guidelines) and a treatment plan agreed. Systemic therapy with either FOLFIRINOX or Gem/Cap was delivered followed by chemoradiotherapy if disease remained localised. Toxicity, response, pathological outcomes and survival were all recorded. A total of 85 patients were included in the study: 45 had initially resectable disease; 19 required a response for resection and 21 had locally advanced inoperable disease; 34 patients underwent resection. The median survival for the potentially resectable group was 22.2 months while for those undergoing resection it was 37 months. We have demonstrated that a neoadjuvant approach is deliverable and tolerable. In addition we have demonstrated impressive survival results in patients undergoing resection with no detriment in outcome for those not proceeding to surgery.

L03 - Role of induction chemotherapy in the multimodal management of locally advanced epithelial sinonasal cancer: a single center experience

Background: outcomes of locally advanced epithelial sinonasal cancer remain unsatisfactory, despite the improvement in surgical approaches and advances in radiotherapy techniques. The incorporation of induction chemotherapy (IC) in the multimodal treatment strategy has shown promising results in few studies. Only limited and heterogeneous data exist on prognostic factors, due to the rarity of this disease. Materials and methods: we reviewed data of 63 consecutive patients (pts) with AJCC stage III-IV epithelial non glandular sinonasal cancer, treated at National Cancer Institute of Milan with IC followed by locoregional treatment between 1996 and 2013. Overall survival (OS) and progression free survival (PFS) were calculated with the Kaplan Meier method. Cox regression analysis was used to determine predictors of OS and PFS. Results: the following histotypes were represented: 25 sinonasal undifferentiated carcinoma (SNUC), 8 pure neuroendocrine cancer (SNEC), 24 keratinizing and not keratinizing squamous cell carcinoma (KSCC + NKSCC), 6 small cell cancer; neuroendocrine differentiation was present in 18 patients. Fifty patients had stage IV and 13 patients stage II-III. After IC, 27 pts were treated with surgery and (chemo)radiation, while 36 pts received chemoradiation. Overall, 53 patients showed a response to IC (PR= 45 CR= 8), 8 had stable disease and 2 had progression. Three-year OS and PFS rates were 73% and 53%, respectively. After stratification according to histological subtypes, 3-year OS rates were 86% for SNUC, 36% for SNEC, 74% for KSCC + NKSCC, and 50% for small cell tumors, respectively. When stratified according to response to IC, patients with a complete response showed a significantly better PFS compared to pts with partial response or stable disease (log-rank test; p 0.0325). Finally, in Cox regression models, patients with a tumoral neuroendocrine differentiation showed a significant worse PFS in respect to patients without neuroendocrine differentiation (HR: 2.8; p = 0.009). Conclusions: response to IC and neuroendocrine differentiation represent prognostic factors in locally advanced epithelial sinonasal cancer treated with a multimodality approach. Efforts are still needed to develop strategies overcoming tumor resistance in order to increase survival. Two phase II trials are ongoing to investigate the role of IC, surgery and photon/heavy ion radiation in these tumors (Clinicaltrials.gov identifier: NCT02099175 and NCT02099188).