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152 Background: In castrate-resistant oligo metastatic prostate Cancer (CRoligoMPC), the benefit of metastases-directed ablative radiotherapy (MDRT) is poorly investigated. Our study retrospectively reviewed the cases of CR oligoMPC treated with MDRT. Methods: Patients receiving MDRT in CRoligoMPC were retrospectively reviewed. Patients were included if: they had < 5 metastases on metabolic work-up, testosterone is < 50 ng/mL, metastases received MDRT. Patients and disease's data were collected: age, Gleason score, time to metastases, time to castration resistance; medical treatments, metastases location (bone versus node); radiotherapy regimens, PSA (PSA doubling time PSADT at the time of MDRT and PSA response). Progression was assessed according to PCWG criteria. PFS and OS are defined as the time from MDRT to first progression, for PFS and death date for OS. Kaplan-Meier analysis was used to summarize time-to-event variables and curves were compared with the log-rank test. A logistic regression was used to identify predictive factors of PFS. Results: the median follow up is 25.6 months.107 patients met inclusion criteria, among those 197 metastases received MDRT. Median age at MDRT time was 73 years. Median hormonosensitivity duration was 38 months (4-225). Forty six patients had metastases at the time of hormonosensitivity and 61 developed metastases in the castration resistance (CR)period (spartan-like population). PSA doubling time at the time of MDT RT was < 12 months in 88%. A median number of 2 metastases per patient was treated (1-4), 54% had RT on bony metastases only, 38% on nodes, 8% on bone + node. In 61 patients with metastases at the time of CRPC, 34.5% received a CR systemic medication before or concomitantly to MDRT, 39% received CR medication at progression, 23.5% never received CR treatment (unknown in 3%). OS is 93% at 2 years and 81.4% at 3 years. For node-only metastases, 2y OS is 100% versus 89% for bone metastases. Median PFS is 12.6 months (IC 95% [9.6; 17]). Metastases location, grade group, PSA or hormonosensitivity duration were not related to PFS in a univariate survival analysis. PFS was 10.2 months when PSA Doubling time was < 6 months, versus 18.2 months when it exceeded 6 months (NS). The PSA 50% response was studied in the Spartan like population, it was 83.4% in patients receiving MDRT AND new generation hormonotherapy; 31% in those who received MDRT without new generation hormonotherapy, and 20% in those who received MDRT at the time of progression of oligometastases occurring under new generation hormonotherapy. Conclusions: In a population of CR oligoM PC with short PSA DT, MDRT leads to a PFS of 12.6 months and to a 3y OS of 81.4%. In this setting, androgen receptor targeting agents are the standard of care. Whether adding MDRT could improve prognosis should be prospectively evaluated.

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

Purpose To investigate the effect of adding concurrent chemotherapy (CT) to cetuximab plus radiotherapy (RT; CT-cetux-RT) compared with cetuximab plus RT (cetux-RT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Patients and Methods In this phase III randomized trial, patients with N0-2b, nonoperated, stage III or IV (nonmetastatic) LA-SCCHN were enrolled. Patients received once-daily RT up to 70 Gy with weekly cetuximab or with weekly cetuximab and concurrent carboplatin and fluorouracil (three cycles). To detect a hazard ratio (HR) of 0.64 for progression-free survival (PFS) with 85% power at a two-sided significance level of P = .05, 203 patients needed to be included in each arm. Results Four hundred six patients were randomly assigned to either CT-cetux-RT or cetux-RT. Patient and tumor characteristics were well balanced between arms, including p16 status. With a median follow-up of 4.4 years, the HR for PFS favored the CT-cetux-RT arm (HR, 0.73; 95% CI, 0.57 to 0.94; P = .015), with 3-year PFS rates of 52.3% and 40.5% and median PFS times of 37.9 and 22.4 months in the CT-cetux-RT and cetux-RT arms, respectively. The HR for locoregional control was 0.54 (95% CI, 0.38 to 0.76; P < .001) in favor of CT-cetux-RT. These benefits were observed regardless of p16 status for oropharynx carcinomas. Overall survival (HR, 0.80; P = .11) and distant metastases rates (HR, 1.19; P = .50) were not significantly different between the two arms. The CT-cetux-RT arm, compared with cetux-RT, had a higher incidence of grade 3 or 4 mucositis (73% v 61%, respectively; P = .014) and of hospitalizations for toxicity (42% v 22%, respectively; P < .001). Conclusion The addition of concurrent carboplatin and fluorouracil to cetux-RT improved PFS and locoregional control, with a nonsignificant gain in survival. To our knowledge, this is the first evidence of a clinical benefit for treatment intensification using cetux-RT as a backbone in LA-SCCHN.

11541 Background: About 47% and 10% of HNSCC occur in pts aged ≥65 or ≥80 respectively. This population being heterogeneous, balancing efficacy with toxicity is challenging. As the G8 screening tool includes 3 nutritional items, we need to evaluate its usefulness in HNSCC pts and to establish an adapted tool for HNSCC pts. Methods: ONCOVAL is the first step of the ELAN program for pts ≥70 with HNSCC not amenable to surgery. Pts were assessed for geriatric frailties before inclusion in appropriate trials (ELAN-RT, FIT, UNFIT) depending on curative or palliative setting and fit or unfit status. The aim was to evaluate the G8 tool and EGE usable by oncologists to classify pts as fit or unfit. The EGE was elaborated by the French GERICO group for HNSCC pts, evaluating functional status, comorbidity, cognition/mood, social status. To estimate sensitivity and specificity of G8 and EGE, we used comprehensive geriatric assessment (CGA) performed by geriatricians as gold standard. Results: From 06/2013 to 08/2018, 633 pts were included in 44 centers. Data are available for 613 pts. Median age 79 years (70-97) with 45% ≥ 80. 75% males. G8 score was ≤14, i.e. at risk of geriatric frailty, in 82% pts. Assessment by EGE was done by physicians (64%), nurses (11%), ELAN staff (21%) in 20 minutes of median time. After EGE, oncologists classified 71% pts as unfit. 49% of pts were assessed by CGA. The G8 score with cut-off ≤ 14 has sensitivity 91% and specificity 30%. Lowering cut-off to 12 increased specificity to 56% but decreased sensitivity to 75%. Sensitivity of EGE was 95% and specificity 60%. Multidisciplinary interventions were more frequently implemented in pts assessed by geriatricians than in others (71% vs 47%), even after adjusting for frailty. 58% of pts included in ONCOVAL were further included in ELAN therapeutic trials. Assessment by geriatricians did not modify the rate of inclusion in trials. Conclusions: The G8 screening tool is not appropriate for HNSCC pts. The EGE was feasible and had better sensitivity and specificity. Oncologists and geriatricians must continue such collaboration to propose tailored treatments. Clinical trial information: NCT03614936.

Purpose To compare the efficacy and safety of induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) or bioradiotherapy (BRT) for larynx preservation (LP). Patients and Methods Previously untreated patients with stage III to IV larynx/hypopharynx squamous cell carcinoma received three cycles of ICT—docetaxel and cisplatin 75 mg/m2 each on day 1 and fluorouracil 750 mg/m2 per day on days 1 through 5. Poor responders (< 50% response) underwent salvage surgery. Responders (≥ 50% response) were randomly assigned to conventional radiotherapy (RT; 70 Gy) with concurrent cisplatin 100 mg/m2 per day on days 1, 22, and 43 of RT (arm A) or concurrent cetuximab 400 mg/m2 loading dose and 250 mg/m2 per week during RT (arm B). Primary end point was LP at 3 months. Secondary end points were larynx function preservation (LFP) and overall survival (OS) at 18 months. Results Of the 153 enrolled patients, 116 were randomly assigned after ICT (60, arm A; 56, arm B). Overall toxicity of both CRT and BRT was substantial following ICT. However, treatment compliance was higher in the BRT arm. In an intent-to-treat analysis, there was no significant difference in LP at 3 months between arms A and B (95% and 93%, respectively), LFP (87% and 82%, respectively), and OS at 18 months (92% and 89%, respectively). There were fewer local treatment failures in arm A than in arm B; salvage surgery was feasible in arm B only. Conclusion There is no evidence that one treatment was superior to the other or could improve the outcome reported with ICT followed by RT alone (French Groupe Oncologie Radiothérapie Tête et Cou [GORTEC] 2000-01 trial [Induction CT by Cisplatin, 5FU With or Without Docetaxel in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma]). The protocol that can best compare with RT alone after ICT is still to be determined.

6500Background: In a previous interim analysis, we found a 7-month median overall survival (OS) benefit (p = 0.002) associated with web-based monitoring to detect recurrence in lung cancer patients...

6015 Background: Concomitant CT-RT is a well established standard of care (SoC) in locally advanced (LA) squamous cell carcinomas of the head and neck (SCCHN). While there is a well established dose effect relationship for RT alone in these cancers, it is not known whether this also applies to concomitant CT-RT. Methods: Patients were randomized between 75 Gy/7 weeks (Arm A) versus 70 Gy/35F in 7 weeks (Arm B). A sequential boost of 10 times 2.5 Gy after 50Gy/25F was given to the initial gross tumor volume (GTV) in Arm A. IMRT was used for arm A and 3D conformal RT for arm B. In both arms, patients (pts) received during RT 3 cycles of cisplatin at 100 mg/m2. Inclusion criteria were pts fit for receiving high dose cisplatin, non metastatic, non operated stage III-IV SCC of oral cavity, oro/hypopharynx. A 1:1 randomization was done by minimization on centers, N & T stages & GTV uni/bilateral. To detect a hazard ratio (HR) of 0.56 in locoregional (LR) control, inclusion of 310 pts was required to observe 109 LR progressions and achieve 85% power at 2-sided significance level of 0.05. Results: Between 2005 and 2015, 188 pts were randomized: 82% males, median age 58 years, 85% oropharynx. The accrual rate was slower than expected, due to the fact that IMRT became a SoC and was only allowed in arm A. As a consequence the trial was discontinued after inclusion of 188 patients. The majority of pts had stage IVa (73% vs 72%). All initial characteristics were well balanced between arms. The median follow-up was 4.7 years, not different between arms. Acute and late xerostomia were markedly improved in arm A (IMRT arm). The 1-year grade 0-1 salivary toxicity (RTOG) was 81% and 34% (p< 0.0001) in arm A and B respectively. At 3 years these rates were 92% vs 53% (p=0.0003). The increase of the dose to the GTV with IMRT did not transfer in a higher LR control probability with an adjusted HR of 0.88 [95%CI 0.51-1.52] (p=0.63). PFS, overall survival were not significantly different between the 2 arms. Conclusions: The dose escalation of RT to the GTV did not improve LR control in patients treated with concomitant CT-RT. This trial adds some new evidence level 1 in favor of IMRT in LA SCCHN. Clinical trial information: NCT00158678.

6002 Background: To compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation. Methods: Ope...

TPS6099 Background: 30% of SCCHN occur in patients (pts) >= 70y and the main challenges in these pts are to cope with the treatment benefit/risk ratio and the tumor related symptoms. However, these pts are usually not included in trials. We developed a large prospective clinical program planed to enroll 448 pts in 3 distinct trials to improve the multidisciplinary management of elderly SCCHN pts. The main objectives of this study are to demonstrate that a geriatric evaluation is feasible in daily practice for SCCHN pts and to set new standards of care in this population. Methods: To be included in one of the three trials, SCCHN pts aged 70 or over, not suitable for surgery, must first be enrolled in ELAN-ONCOVAL study where they are classified as fit or unfit, using a geriatric evaluation applicable to the daily practice. Comprehensive Geriatric Assessment is optional. In curative situation, unfit pts are proposed to be enrolled in the randomized non-inferiority ELAN-RT trial, comparing standard radiother...

5505 Background: Cetuximab in combination with platinum and 5FU (PFEx) has become a standard in first-line treatment of patients (pts) with R/M SCCHN. Cetuximab and taxane combinations have shown promising activity. This multicenter phase II study evaluates the efficacy and safety of cetuximab, docetaxel and cisplatin combination (TPEx) as first-line treatment in pts with R/M SCCHN. Methods: Pts were required to have WHO PS 0-1, no prior systemic therapy for R/M SCCHN, cumulative dose of cisplatin less than 300 mg/m² and no prior anti-EGFR therapy. Pts received docetaxel 75 mg/m² day 1, cisplatin 75 mg/m² day 1 and cetuximab (400 mg/m² on day 1 of cycle 1 then 250 mg/m² weekly), repeated every 21 days x 4 cycles then followed by cetuximab 500 mg/m² every 2 weeks (wks) as maintenance therapy until disease progression or unacceptable toxicity. G-CSF support with lenograstim 150 µg/m²/day was delivered after each cycle of chemotherapy. Response was assessed every 6 wks, according to RECIST. The primary endpoint was objective response rate (ORR) at 12 wks. Secondary endpoints were safety, best overall response, progression-free survival (PFS), overall survival (OS) and biomarkers. Results: 54 pts have been enrolled: 52 males, median age 57.8years (28-69), 12 (22.2%) oropharynx, 55% metastatic.48 pts could be evaluated for ORR at 12 wks: partial response, stable disease and progression were respectively found in 23 pts (PR 47.9%), 21 pts (SD 43.7%) and 4 pts (PD 8.3%). Best overall ORR was 54% (1 CR, 27 PR). The median PFS and OS were 7.1 and 15.3 months, respectively. The 1-year OS was 58.6%. Median PFS after start of maintenance therapy was 4.2 months. Toxicity was manageable with G-CSF support. Treatment related toxicities included G4 neutropenia (n=3). Grade 3 events were skin rash (n=5), hypersensitivity reaction (n=3), mucositis (n=1), fatigue (n=1) and febrile neutropenia (n=1). Alopecia was common. 1 toxic death was related to sepsis on feeding tube. Conclusions: Efficacy analysis demonstrates that TPEx regimen is effective and might be a relevant substitute for PFEx as first-line treatment in fit pts with R/M SCCHN.

5516 Background: The purpose of this study is to report long-term results of a randomized study designed to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV oropharynx carcinoma. Methods: Between July 1994 and September 1997, 226 patients with locally advanced oropharynx stage III and IV tumors have been entered in a phase III multicentric randomized trial comparing RT alone (arm A, 115 patients) to RT with concomitant CT (arm B, 111 patients). RT was identical in the two arms, delivering 70 Gy in 35 fractions. In arm B patients received simultaneously on d1, d22 and d43, 3 cycles of a 4 day regimen containing carboplatin (70 mg/m2/d) and 5FU (600 mg/m2/d) continuous infusion. 34% were stage III and 66% were stage IV. The 2 arms were equally balanced regarding to age, gender, stage, performance status, histology, tumor biology, and primary tumor site. Results: Results have been published in 19...

6010 Background: Induction chemotherapy (ICT) followed by irradiation (RT) and concurrent chemoradiotherapy (CRT) are validated options for LP. Docetaxel-based ICT, concurrent cetuximab and RT are new options and SCRT (ICT followed by CRT) has been reported as a potential new approach. However, to date there are no data assessing SCRT specifically for LP. Methods: Previously untreated patients (pts) with larynx or hypopharynx squamous cell carcinoma and candidates for a total laryngectomy were eligible for this randomized phase II study. Eligible pts received 3 cycles of ICT (docetaxel and cisplatin both 75 mg/m2 on day 1 and 5-FU 750 mg/m2/day on days 1–5). In case of response ≥ 50 % pts were randomized to receive either in arm A: RT (70 Gy) with cisplatin (100 mg/m2 on days 1, 22 and 43 of RT) or in arm B: Cetuximab (400 mg/m2 loading dose before RT and 250 mg/m2 on the first day of the 7 weeks of RT. Pts with response < 50% had salvage surgery. Primary endpoint was LP 3 months after treatment, secondary endpoints were larynx function preservation at 18 months, quality of function and tolerance to treatment. Results: From March 2006 to April 2008 (end of accrual), 153 pts with stage III-IV larynx/hypopharynx cancer were enrolled in the study and could start ICT. Of them 74 % could receive the planned ICT while the others had either reduced dosages or less than 3 cycles. Toxic deaths occurred in 3 pts (2%). Of the 147 evaluable pts after ICT, 22 were non-responders (15%), 4 pts were withdrawn from the study, 6 responding pts with ICT-related toxicity precluding any further cisplatin could not be randomized and finally 115 pts could be randomized (59 in arm A and 56 in arm B). 3 months after treatment there was no significant difference in LP (93% in arm A and 96% in arm B). In arm A, 45 % of pts could receive the full CRT protocol vs 71 % in arm B. In arm A 50% of pts had cisplatin-related toxicity (definitive in 52% the cases) while in arm B 26 % of patients had cetuximab-related toxicity (definitive in only 1 case). There was no CRT treatment-related death. Conclusions: SCRT is considered for LP. ICT followed by RT with concurrent cetuximab appeared better tolerated than with concurrent cisplatin with the same LP rate 3 months after treatment. [Table: see text]

5506 Background: Induction chemotherapy (CT) with PF followed by RT in case of objective response is an alternative to total laryngectomy (TL) for patients with locally advanced larynx (L) and hypopharynx (H) cancer. Data have suggested that T may add to the efficacy of PF. The objective of this trial was to determine whether the addition of T to PF could increase the L preservation rate. Methods: Patients with L and H cancer for whom surgical procedure required TL were randomized to receive PF or TPF. Inclusion criteria were: adequate organ function, WHO PS 0 or 1, age from 18 to 70, signed informed consent. Treatment arms were PF = P 100 mg/m2/d1 and F: 1000 mg/m2 continuous infusion (CI) d1 to 5, TPF = T: 75 mg/m2/d1, P: 75mg/m2/d1 and F: 750mg/m2 CI d1 to 5 for 3 cycles with 21 days interval. Patients with complete or partial response and who recovered normal L mobility received RT to 70 Gy. Non responders underwent TL followed by RT. The primary endpoint was 3-year larynx preservation rate. To detect an absolute difference of 15% the sample size was 210. Results: 220 patients were randomized (108 to PF, 112 to TPF). Patients characteristics (age, sex, PS, primary site, TN) were well balanced. The TPF arm showed greater grade 3–4 alopecia (19% vs 2%) and neutropenia (57% vs 35%) while the PF arm showed greater grade 3–4 mucositis (9% vs 4%) and febrile neutropenia (6% vs 2%).Compliance to CT was better in the TPF. The specified treatment was delivered in 81.2% of patients in the TPF vs 67.4%. The overall response rate (T and N) was 82.8% in the TPF vs 60.8% (p = 0.0013). 60.6% of patients achieved a complete endoscopic response vs 46.7%. L preservation was offered for 80% of patients in the TPF vs 57.6%. A high hemoglobin level (>14 gr/l) and a compliance to treatment >80% are associated with a better response rate. With a median follow up of 35 months the 3-year actuarial L preservation rate is 73% following TPF vs 63% using the PF regimen. Conclusion: In advanced L and H cancer, TPF demonstrated significantly superior overall response rate compared to the PF regimen. The TPF is better tolerated and preliminary results suggest that L preservation could be achieved for a higher proportion of patients. No significant financial relationships to disclose.