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Laryn-conserv-slides-050209 - Laryngeal Conservation...

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Unformatted text preview: Laryngeal Conservation Laryngeal Sarah Rodriguez, MD Shawn Newlands, MD UTMB Dept of Otolaryngolgy Grand Rounds February 2005 Introduction Introduction Advanced stage glottic cancer traditionally Advanced has been treated with surgery, most often total laryngectomy, and post-operative radiation therapy (PORT) radiation Several randomized trials have Several demonstrated the feasibility of organ preservation in patients with advanced laryngeal and hypopharyngeal cancer laryngeal Landmark Studies Landmark The Department of Veterans Affairs The Laryngeal Cancer Study Group (1991) Laryngeal The European Organization for Research The and Treatment of Cancer (1996) and Radiation Therapy Oncology Group Trial Radiation 91-11 (2003) 91-11 VA Study VA Goal: to investigate whether induction chemotherapy and definitive XRT with laryngectomy reserved for salvage for patients with stage 3 or 4 laryngeal cancer represented a better initial treatment approach than total laryngectomy and post-operative XRT post-operative VA study Design VA Two arms (322 patients divided between Two groups): groups): Experimental arm Patients received two cycles of chemotherapy consisting of Patients cisplatin and fluorouracil; those found not to have at least a partial response at the primary site went on to laryngectomy; the remainder received a third round of chemotherapy and the vast majority of these patients went on to definitive XRT the Control arm Patients received total laryngectomy and standard postoperative radiation therapy (PORT) VA study results VA The larynx was preserved in 107 patients (64%) of those The assigned to induction chemotherapy assigned 59 underwent total laryngectomy: 30 prior to XRT and 29 after 59 radiation (persistent disease present on planned endoscopy 12 weeks after XRT) weeks Late salvage surgery required in 11 additional patients (80% of Late these occurred in the year after treatment) these Salvage laryngectomy required more often in those with glottic Salvage vs supraglottic CA (43 vs 31%); fixed vs mobile VCs (41 vs 29%); gross cartilage involvement vs no cartilage involvement (41 vs 35%)--but all this not statistically significant (41 Significantly, salvage surgery was required in 44 % of pts with Significantly, stage IV cancers as compared with 29% of pts with stage 3 cancer AND 56% of patients with T4 cancers as compared with 29% of patients with smaller primaries 29% Other VA study Findings Other The estimated two year The survival was 68% for the induction chemotherapy group and the surgery group. No significant differences in survival between treatments when pts grouped according to tumor stage or site. tumor Survival rates similar for Survival chemotherapy responders and non-responders non-responders Patients in the induction Patients chemotherapy arm had a higher rate of local failure but a decreased rate of distant metastases metastases EORTC Study EORTC Goal: To compare the results of treating patients with T2-T4, N0-N2b squamous cell carcinoma of the pyriform sinus or aryepiglottic fold with either induction chemotherapy followed by radiation or standard surgical therapy and PORT standard EORTC Patients EORTC 94 patients randomized to the immediate 94 surgery arm surgery 100 patients randomized to the induction 100 chemotherapy (cisplatin and fluorouracil) and XRT arm and Patients in the induction chemo arm had to Patients have a complete response in order to proceed to XRT proceed EORTC Results EORTC Survival: Disease-free survival at 3 and 5 years Disease-free essentially the same for the chemotherapy and immediate surgery arms: 43 and 25% for chemo arm and 32 and 27% for surgery arm chemo At three years the overall survival rates At appeared to favor the chemotherapy arm; the survival rates at 5 years were similar between groups but this estimate based on small number of patients at risk number EORTC Results, Laryngeal Preservation Preservation For the entire group of 100 patients randomized For to induction chemotherapy, the rate of being alive and having a functional larynx at 3 and 5 years was 28 and 17% respectively years The 3 and 5 year rate of retaining a functional The larynx in the patients who completed treatment in the induction chemotherapy arm were 64% and 58% respectively and EORTC Observations and Conclusions Conclusions The authors conclude that attempted larynx The preservation with induction chemotherapy is acceptably safe with hypopharyngeal cancer acceptably Fewer distant mets and increased time to distant Fewer mets in the chemotherapy arm mets Chemotherapy complete responders were more Chemotherapy frequent among those with T2 disease (82%) than those with T3 (48%) or T4 (0%) disease than Summary of VA and EORTC studies studies Both trials suggest that organ preservation is Both possible in patients with advanced stage laryngeal or hypopharyngeal cancer; laryngeal The role of chemotherapy not elucidated; rates The of organ preservation in the VA trial similar to published rates of organ preservation after radiation alone radiation Distant metastases appear to be decreased with Distant chemotherapy chemotherapy Suggest that head and neck squamous cell Suggest carcinoma is sensitive to cisplatin and fluorouracil fluorouracil RTOG 91-11 RTOG Goal: To investigate three radiation-based To therapies in the treatment of stage 3 and stage 4 laryngeal cancer: Induction cisplatin and fluorouracil followed by Induction XRT (identical to VA experimental arm protocol) protocol) Concurrent chemoradiation with cisplatin Standard radiotherapy Patients Patients Eligible patients Eligible had stage 3 or 4 laryngeal cancer. T1 primary tumors were ineligible as well as T4 tumors that penetrated through cartilage or more than 1 cm into the base of tongue. tongue. RTOG 91-11 Results RTOG The rate of laryngeal preservation at a median follow-up of 3.8 years The was significantly higher among patients receiving radiotherapy with concurrent cisplatin (84%) than among those receiving induction chemotherapy followed by XRT (72%) or those receiving radiotherapy alone (67%) radiotherapy Chemotherapy suppressed distant metastases Two and five year survival did not differ among treatment groups Patients who were treated with concurrent chemoradation had Patients significantly fewer local failures than either induction chemotherapy + XRT or radiotherapy alone XRT Two and five year disease free survival estimates Arm one: 52 and 38% Arm two: 61 and 36% Arm three: 44 and 27% Areas of Interest Areas Timing of combined chemoradiotherapy Other chemotherapeutic agents New biologic agents EGFR monoclonal antibodies Targeting hypoxic cells Altered radiation fractionation schedules Hyperfractionation: lower doses per fraction, more Hyperfractionation: fractions per day; increased dose of radiation; same duration of therapy; reduces late toxicity duration Accelerated fractionation: same dose over a shorter Accelerated period of time; increases acute toxicity; decrease tumor repopulation tumor Quality of Life and Functional Outcomes Outcomes If both surgery + PORT and If chemoradiation yield good local control and essentially equivalent survival rates, what is the comparative quality of life for the patient? the What kinds of functional outcomes can be What expected after aggressive organ preservation protocols? preservation VA Study Revisited: Quality of Life VA A 1998 follow-up to the VA study identified 25 surviving 1998 patients from the surgery + PORT group and 21 patients from the induction chemo + XRT group. Patients were administered the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, the Medical Outcomes Short-Form 36 (SF-36), and the Beck Depression Inventory (BDI) Depression Chemo/XRT patients had significantly better quality of life scores Chemo/XRT on the SF-36 mental health domain and also had better HNQOL pain scores pain Patients with intact larynges had significantly better HNQOL Patients emotion scores emotion More patients in the surgery (28%) were depressed than in the More chemo/XRT group (15%) chemo/XRT Other Quality of Life Studies Other Lee-Preston 36 patients surveyed 3-12 months after treatment with radiotherapy only 36 (24) total laryngectomy + PORT or salvage laryngectomy after XRT (12) (24) Functional Assessment of Cancer Therapy (FACT) with head and neck Functional subscale, Nottingham Health Profile and the Hospital Anxiety and Depression Scale Depression Combined therapy patients had lower FACT head and neck scores Combined (poorer QOL) with identified problems of dry mouth, swallowing, breathing and communication breathing The two treatment groups showed no difference in anxiety but there The was a trend towards greater depression in the combined therapy group was Results of the NHP show that scores were worse for those in the Results combined therapy group in all domains except pain. The differences were statistically significant in the emotional reaction and social isolation subscales. subscales. Other Quality of Life Studies Other Hanna EORTCQOL administered to 42 patients treated EORTCQOL either with concurrent chemorad or surgery and PORT for stage 3 or 4 laryngeal cancer PORT No statistically significant differences in overall QOL No scores scores Subscale analysis revealed a trend for pts in the Subscale surgery group to experience greater difficulties with social functioning relative to the chemorad group social Surgery pts reported significantly greater sensory Surgery disturbances, use of painkillers, and coughing disturbances, Chemorad pts reported significantly greater problems Chemorad with dry mouth with Functional Outcomes/Speech Functional VA Study: patients who retained their larynx fared VA significantly better from the standpoint of speech communication. At two years post-treatment, patients who retained their larynx At had regained their pre-treatment level of functioning for two of the three measures tested (intelligibility and reading rate) and exceeded pretreatment performance on the third ( a communication profile used to assess general communication status). Laryngectomy patients had a decrease in all three measures Laryngectomy despite all options of speech rehabilitation and therapy despite RTOG No difference in treatment groups The reporting of moderate or worse speech impairment was The reported as 6, 11, and 13% at one year and 3, 6 and 8 percent at two years two Functional Outcomes/Swallowing Functional RTOG At one year, 23% of those assigned to concurrent At chemorad could swallow only soft foods or liquids and 3% could not swallow at all 3% At one year only 9% of the induction chem/rad group At was limited to soft foods or liquids and there were no patients that could not swallow at all. This was similar to the radiotherapy-only arm to All three groups were similar at two years with 1416% of patients reporting difficulty swallowing Functional Outcomes/Swallowing Outcomes/Swallowing Gillespie recently reported a survey of pts 12 months or more out from Gillespie treatment of stage 3 or 4 SCCA of the oropharynx, larynx or hypopharynx. 19 patients were in the larynx/hypopharynx category. 11 of these were treated with surgery + PORT; 8 were treated with concurrent chemoXRT treated MD Anderson Dysphagia Inventory was used Global subscale: pts perception of degree of swallowing impairment Emotional subscale: upset or embarassement by dysphagias Functional subscale: ease of food preparation and eating in public Physical subscale: effect of dysphagia on dietary consistency, Physical aspiration, weight maintenance aspiration, No difference between in scores between treatment type All pts in study had scores 25-50% worse than the general population Functional Outcomes/Speech and Swallowing Swallowing Carrara de Angelis reports speech and swallow Carrara evaluations of 19 patients who underwent concurrent chemoradiation with paclitaxel and cisplatin for larygeal or hypopharyngeal SCCA cisplatin Analysis took place 2-9 mos post-treatment 11 pts with tracheostomy and 14 pts with feeding tube 11 at some point in treatment at At time of analysis, 6 still had tracheostomy and 6 At were still using a feeding tube were Results 40% of patients with moderate dysphonia, 27% 40% severe dysphonia severe More Carrara de Angelis Results More DYSPHAGIA SEVERITY DYSPHAGIA 1. Severe (feeding tube): unable to tolerate any oral contrast 1. safely safely 2. Moderate to severe (not permitted oral intake): maximum 2. assistance or use of strategies with partial oral contrast only (tolerates at least 1 consistency safely with total use of strategies) strategies) 3. Moderate (modified diet and/or independence): total 3. assistance, supervision, or strategies, 2 or more diet consistencies restricted consistencies 4. Mild to moderate (modified diet and/or independence): 4. intermittent supervision or cueing, 1 or 2 consistencies restricted restricted 5. Mild (modified diet and/or independence): distant 5. supervision, may need 1 diet consistency restricted supervision, 6. Within functional limits or modified independence (normal 6. diet): patient may have mild delayed swallowing reflex, stasis spontaneously cleared, and there is no penetration or aspiration aspiration 7. Normal (normal diet): normal in all situations and the 7. patient does not need strategies or extra time patient Other Functional Outcome Studies Other Staton Identified 45 patients available for follow-up 6 months after Identified treatment with intra-arterial cisplatin and concurrent XRT for stage 3 or 4 laryngeal cancer stage Sixteen patients required a tracheostomy and/or gastrostomy Sixteen (tracheostomy 13, gastrostomy 13, both 10) (tracheostomy The only variable found to impact subsequent tracheostomy and The feeding tube requirement was vocal cord fixation. T4 status and massive cartilage invasion both trended toward an association with laryngeal dysfunction with Conclusions: Quality of Life and Functional Outcome Functional Existing studies are small groups measured on different Existing instruments instruments Data on quality of life seem to favor chemoradiation for organ Data preservation preservation If rates of disease control are equal, more weight should be If given to individual patient factors in determining treatment given What is the comparative quality of life in those that require What surgical salvage? surgical More data is required on how many patients require long-term More tracheostomy or gastrostomy after chemoradiation and how these specific issues impact QOL these More data is required on swallowing function post-treatment More to determine normal time course of improvement and impact on QOL on Surgical Complications After Attempted Organ Preservation Attempted Danish Study 472 patients treated with post-irradiation salvage laryngectomies 89 fistulae lasting more than two weeks=rate of 19% The number of laryngectomies performed per year declined and the fistulae rate The increased; risk of fistula in 1987 12% vs risk of fistula in 1997 of 30% increased; RTOG No significant difference in the rate of systemic complications Fistulae developed in 25, 30 and 15% of patients in arms 1, 2 and 3 respectively Lavertu Compared complications of a group of patients treated for stage 3 or 4 head and Compared neck SCCA with either XRT or concurrent chemo/XRT neck 30 salvage procedures were done with total laryngectomy being part of the 30 salvage procedure in 14 salvage Major complications included carotid artery rupture, fistula, and GI bleed (one of Major each in the radiotherapy-only group) AND sepsis, stroke and pharyngeal stenosis (one each in the chemo/rad group) stenosis Minor complications were not numerous and did not differ between groups Author concludes that major and minor complications did not differ between Author groups and that morbidity rates for salvage surgery after aggressive organ preservation protocols was acceptable preservation Conclusions Conclusions More patients with advanced disease can enjoy More organ preservation organ Work is ongoing to define the ideal protocols for Work organ preservation organ More work needs to be done to define which More patients are acceptable for aggressive organ preservation and what quality of life and functional outcomes they can expect functional Role of the surgeon is changing Medical oncologist should come to tumor board ...
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