6 Patients with asymptomatic, advanced stage, follicular lymphoma have shown no benefit of immediate chemotherapy when compared with a watchful-waiting approach, whereby chemotherapy is deferred until disease progression. Deferring chemotherapy may spare the patient the side effects of the chemotherapy in the short term and historically this has been the preferred approach. With the advent of rituximab and its relatively favourable side effect profile we designed this study to compare a watchful waiting approach with immediate treatment with rituximab. Adult patients with asymptomatic stage 2, 3 or 4 follicular lymphoma (grades 1–2 & 3a) and adequate bone marrow reserve were randomly assigned with a ratio 1:1:1 to watchful waiting (arm A) or rituximab 375mg/m2 weekly for 4 weeks (arm B) or rituximab 375mg/m2 weekly for 4 weeks followed by rituximab maintenance every 2 months for 2 years (starting at month 3 until month 25)(arm C). The primary endpoints were a) time to initiation of new therapy (chemotherapy or radiotherapy) and b) effect on quality of life. The study was designed to detect an improvement in the median time to initiation of therapy in each of the rituximab arms of 18 months (from 30 months to 48 months) with 2.5% significance level and 90% power. A total of 230 events were required and 600 patients were planned. In September 2007, a decision was made to discontinue arm B as evidence of the efficacy of maintenance rituximab became clear. With the two arms comparison, using a significance level of 5%, a total of 360 patients in Arm A and Arm C were planned. Between September 2004 and May 2009 462 patients were randomised (186 Arm A, 84 Arm B, and 192 Arm C). 95% of patients had low tumour burden (GELF criteria) the other 5% had raised LDH but fulfilled the remaining GELF criteria. 98% were entered into the study within 4 months of diagnostic biopsy. Median age 60yr (range27-87). 54% female. ECOG performance status 0=91% & 1=9%. Grade 1–2=89%. Stage 2(21%), stage 3(40%), stage 4 (39%). 42% had bone marrow involvement. FLIPI score: 0=9%, 1=26%, 2=41%, 3=22%, 4=2%. In March 2010 the Data Monitoring committee concluded that the data regarding time to initiation of new therapy was mature and recommended full analysis of data to be performed and presented in the knowledge that rituximab maintenance was still ongoing in 20 patients. To date 45 SAEs have been reported (Arms A=14, B=6, C=25), 14 SAE were considered possibly, probably or definitely related to the study drug (Arm B=4, C=10). 5 allergic reactions (two grade 3), 6 infections, 3 episodes of grade 4 neutropenia. Responses were assessed at month 7, 13 and 25. CT was compulsory at months 7 and 25. Bone marrow was only required if CR on clinical and CT criteria. An interim analysis was performed on 9 Feb 2010. At month 7: Arm A: spontaneous remission was seen in 3%, PR=6%, NC (no change) =74%, PD=17%. Arm B: CR+CRu=45%, PR=33%, NC=19%, PD=3%. Arm C: CR+CRu=49%, PR=36%, NC=11%, PD=3%. At the time of the interim analysis 93 (20%) patients had initiated new treatment. Of these 93 patients 84 (90%) had clinically reported progression. New treatment was chemotherapy in 78 (84%), radiotherapy in 10 (11%), rituximab monotherapy in 2 (2%), surgery in 1(1%),currently not known in 2 (2%). The estimated median time to initiation of new therapy in arm A was 33 months, similar to our previous trial of watchful waiting (Ardeshna et al Lancet 2003). The time to initiation of new therapy was significantly longer in the rituximab arms (fig 1, p value of log-rank test <0.001 for each of rituximab arms vs arm A) and the median time was not reached at 4 years. Not all patients who were reported to have clinically progressed (n=142) warranted initiation of therapy (n=84). There were again significant differences in progression-free survival between the observation and rituximab arms (fig 2, p value of log-rank test <0.001 for each of rituximab arms vs arm A). 98% of patients remain alive and there was no different in overall survival between the 3 arms (p value >0.5). These data indicate that initial treatment with rituximab significantly delays the need for new therapy and this finding may change the management of patients with newly diagnosed asymptomatic follicular lymphoma. Disclosures: Ardeshna: Roche: Funding data manager, Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Rituximab is currently not licensed for use as a single agent in previously untreated patients with with asymptomatic advanced stage follicular lymphoma. Pocock:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cunningham:Roche: Research Funding. Davies:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; chugai: Honoraria, Research Funding. Walewski:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Linch:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees.

DIN is a mild form of LC1 and is considered a normal anatomical variant. Recent cohort studies demonstrate IL to be a safe, low-risk, and efficacious treatment of LC1, but few studies focus on DIN. We present results from two aerodigestive clinic (ADC) pilot studies at our institution, in patients 1-3 years old, with DIN-related dysphagia and aspiration (DA). Feeding, respiratory-related symptom scores, and aspiration/penetration assessed on modified barium swallow (MBS) significantly improved following combined IL and feeding therapy using a thickener weaning protocol (TWP). Subgroup analysis reveals combined IL and TWP to be particularly effective in patients with severe baseline DA. Multidisciplinary aerodigestive evaluation and management with IL and feeding therapy focused on weaning levels of thickener is emerging as a novel and effective approach for treatment of DIN-related DA in young children. Further comparative, prospective trials investigating effects of IL and feeding therapy are required to validate results.

Objectives: Deep interarytenoid notch (DIN) is a congenital variation of the larynx often associated with dysphagia and aspiration (DA) in young children. Feeding therapy with thickeners and surgical management with injection larygoplasty (IL) are used with various efficacies. Thickeners address the functional domain and IL addresses the anatomical domain of treatment. Our objective was to evaluate DIN patients managed with both interventions. Methods: We conducted a retrospective pilot descriptive study of DIN patients with DA aged 1-3 years receiving thickeners and IL. Patients received a systematic weekly reduction of thickeners based on clinical signs and symptoms of DA. The outcomes were assessed by the rate of thickener level reduction and DA-related sign/symptom frequency achieved at 6 months post-treatment.Results: Thirteen patients with DIN associated DA were analyzed. Thickener scores improved from an average of 5.76 (3/4 honey) to 2.15 (thin) (p = 0.001). DA-related signs/symptoms frequency improved from an average of 3.3 to 0.84 (p = 0.05).Conclusions: These findings suggest that treatment of DIN associated DA with a combination of thickeners and IL results in significant clinical improvements in young children.

Children in the IFT cohort experienced a median reduction in ETN dependence of 49% (34.5-58.5%) compared with a median reduction of 0% (0-25%) for TT (p > 0.0001). Almost half of the IFT cohort no longer required ETN by the conclusion of the 5-week program. Medically complex young children (median age 26 months) successfully reduce or eliminate ETN in an outpatient multidisciplinary intensive feeding program.