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PO-089: The Self-Care Rehabilitation in the Patients with Head and Neck Cancer Treated with Definitive Radiotherapy
4th ICHNO literature, to our knowledge this is the first series directly comparing feeding tube dependence in patients treated with 3DCFRT versus IMRT. PO-087 DELAYED ORAL MUCOSA INJURY AFTER RADIOTHERAPY FOR HEAD AND NECK CANCER ASSESSED BY EXFOLIATIVE ORAL CYTOLOGY P. Massaro1, F. Corbella1, R. Di Liberto2, A. Paolini3, F. Pasi4, C. Tinelli5, A. De Silvestri5, R. Nano4 1 I.R.C.C.S. Policlinico San Matteo, S. C. Radioterapia Oncologica, Pavia, Italy 2 I.R.C.C.S. Policlinico San Matteo, S.C. Fisica Sanitaria, Pavia, Italy 3 I.R.C.C.S. Policlinico San Matteo e Università degli Studi di Pavia, S.C. Fisica Sanitaria e Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", Pavia, Italy 4 Università degli Studi di Pavia, Dipartimento di Biologia e Biotecnologie "Lazzaro Spallanzani", Pavia, Italy 5 Fondazione IRCCS Policlinico San Matteo, Servizio di Biometria e Statistica, Pavia, Italy Purpose/Objective: Radiotherapy for head and neck (H&N) district malignancies may induce damage to oral mucosa leading to bothersome side effects during therapy and permanent oral sequelae; little is known about long term mucosal alterations after completion of radiotherapy course. In our study, late oral mucosal toxicity after radiotherapy for H&N cancer has been assessed by exfoliative oral cytology. Materials and Methods: Eligibility criteria were: age between 30 and 80, a minimum of two-years follow-up after completion of 3D conformal radiotherapy for H&N solid tumors, with oral mucosa in the fields of exposure of therapy. From December 2011 to July 2012, 25 consecutive patients were enrolled at their programmed follow-up visit. They were 21 males and 4 females, mean age was 61.7 years (range 46-76), mean follow-up after radiotherapy was 28.9 months (range 24–39), mean dose was 66.6 Gy (range 5070.2) with conventional fractionation, median overall treatment time was 59 days (range 44-88). Tumor prevalent localization was oropharynx and oral cavity (18 out of 25 patients); prevalent histology was squamous (21 out of 25 patients). Thirteen underwent postoperative radiotherapy and 21 patients received chemotherapy (20 concomitant chemo-radiotherapy, 1 sequential chemo-radiotherapy). Smears were collected by scraping right and left cheek mucosa with wooden tongue spatulas, then transferred to 4 dry glass slides (2 for each cheek), fixed immediately with Biofix® and stained with modified May Grunwald Giemsa staining. Smears were examined under 400X power using a light microscope. Results: All the smears collected showed cytological alterations: a characteristic 'folding' appearance of epithelial cells, a peculiar cellular phenotype marker of radiation injury, with enlarged and hypertrophic nucleus. In order to graduate the presence/absence of this specific cellular phenotype, we counted the 'folding' cells as a percentage of all cells per dry glass slide for each cheek, made the average and finally scored them. In almost all the smears we also observed an inflammatory background with neutrophils and lymphocytes not even sustained by an infectious milieu. In our cytological samples, both in right and left cheek mucosa, the presence of inflammation influences the score (i.e. the percentage of 'folding' cells) in terms of a lower score if inflammation is present (Spearman's rho = -0.5064, p value= 0.0098 for right cheek, Spearman's rho = -0.4414, p value= 0.0272 for left cheek). Conclusions: In the late setting after completion of radiotherapy, local inflammatory background has a potential role of scavenger of 'folding' cells, which would represent a label of radiation chronic injury to oral mucosa. We can hypothesize that immune system plays a key role in the variability of individual response of oral mucosa to radiation
S37 damage; our data need to be supported by further investigations. PO-088 ACUTE TOXICITY IN HEAD AND NECK CANCER PATIENTS TREATED WITH CHEMORADIATION/CETUXIMAB ± CONSOLIDATION CETUXIMAB O. Riesterer1, K. Bertogg1, B. Shrestha1, S. Weber1, C. Glanzmann1, G. Studer1 1 University Hospital Zurich, Radiation Oncology, Zurich, Switzerland Purpose/Objective: Cetuximab, an anti-EGFR antibody, is a potent enhancer of tumor response when given concurrently with radiotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). Own preclinical data suggest that cetuximab consolidation after radiotherapy targets residual tumor cells in irradiated tumor bed (Riesterer et al, Radiother Oncol 92(3): 383, 2009). Based on this concept a translational research study was launched at the University Hospital Zurich. Materials and Methods: In this phase II study 60 patients with locoregional advanced HNSCC (stage T3-4 Nx or Tx N2b-c (at least 3 nodes) and/or GTV>70cc are treated with standard chemoradiation (IMRT 70 Gy, cisplatin 40mg/m2 weekly) in combination with concurrent cetuximab (loading dose 400mg/m2, then 250mg/m2 weekly). Thereafter patients are randomized to cetuximab consolidation (500 mg/m2 biweekly for 6 infusions) or no consolidation treatment. Integrated into this study is a translational research project with assessment of tissue, serum and imaging biomarker endpoints. Acute toxicity according to CTCAE version 4.03 was assessed weekly during the concurrent and biweekly during the consolidation phase until 14 weeks after end of radiation. Results: So far 20 patients have been included into the study. Two patients withdrew informed consent because of symptoms associated with acne-like-rash grade 3. In one patient consolidation cetuximab was stopped because of decompensated liver cirrhosis grade 4. 16 patients, who completed treatment, are evaluable for the acute toxicity assessment (male/female=15/1, median age 61 y (48-75)). The median GTV size was 54cc (5-100). The median number of infusions given are: cisplatin: 6 (4-6), concurrent cetuximab: 8 (5-8) and consolidation cetuximab: 6 (1-6). The following grade 3 acute toxicity has been observed: mucositis 50% (8/16), dysphagia 56% (9/16), weight loss 6% (1/16), radiation dermatitis 75% (12/16), acne-like rash 12% (2/16), neutropenia 43%, thrombopenia 6% (1/16), infections 6% (1/16). PEGs were inserted in 56% of patients. Tumor response so far is encouraging with only one histologyconfirmed local tumor persistence in a patient with T3N2c hypopharyngeal cancer. Conclusions: Trimodality treatment with chemoradiation and cetuximab is feasible and does not induce higher acute toxicity than expected with chemoradiation alone. Updated data will be presented at the conference. PO-089 THE SELF-CARE REHABILITATION IN THE PATIENTS WITH HEAD AND NECK CANCER TREATED WITH DEFINITIVE RADIOTHERAPY V. Yurut-Caloglu1, F. Ozdemir2, M. Caloglu1, S. Yavuz3, S. Egrenci1 1 Trakya University Medical Faculty, Radiation Oncology, Edirne, Turkey 2 Medipol University Mega Hospitals Complex, Physiotherapy and Rehabilitation Department, Istanbul, Turkey 3 Trakya University Medical Faculty, Physiotherapy and Rehabilitation Department, Edirne, Turkey Purpose/Objective: The restricted mouth opening (trismus)without temporamandibular joint invasion- is an important late adverse effect of radiotherapy in patients with head and neck cancer. The aim of this study is to determine whether
S38 rehabilitation therapy provides any therapeutic effect on mouth opening in these patients cohort after radiotherapy. Materials and Methods: Fifty-four consecutive patients with squamous cell carcinoma of the head and neck treated with radiotherapy and/or chemotherapy were included in this study. All patients had at least three months since the end of radiotherapy. Mouth opening distance (MOD) ≤35 mm was defined as trismus. MODs were measured twice, once at the beginning of study and once after three months of exercise. Results: Median age was 59 years (range; 31-84). The mean MOD was 37.1 mm (range; 8-62 mm) at the beginning and 38.5 mm (range; 10-62 mm) after physiotherapy (p<0.0001). These values were 30.5 mm (range; 8-35 mm) and 33.4 mm (range; 10-40 mm) in patients with trismus (p<0.0001 respectively); and were 42 mm (range 37-62 mm) and 42.3 mm (range 37-62 mm) in patients without trismus (p=0.009, respectively). The mean MOD were significantly lower in patients who received concurrent chemotherapy (p=0.032) and with higher T stage (p=0.004) at the beginning. Physiotherapy significantly improved the MODs of patients either received concurrent chemotherapy (p<0.0001) or not received (p<0.0001). The mean MOD increased significantly in patients with T1 (p=0.006), T2 (p=0.002), and T4 (p=0.001) tumor stage by physiotherapy but not in patients with T3 (p>0.05). Conclusions: The self rehabilitation method was an effective method for trismus treatment in head and neck cancer patients after definitive radiotherapy. PO-090 SMALLER MARGINS DO MATTER IN RADIOTHERAPY FOR LARYNGEAL CANCER C. Terhaard1, C.A.J.M. Vugts2, M.E.P. Philippens1, N. Kasperts1, F. Pameijer3, C.P.J. Raaijmakers1 1 UMC Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands 2 Institute Verbeeten, Radiation Oncology, Tilburg, The Netherlands 3 UMC Utrecht, Department of Radiology, Utrecht, The Netherlands Purpose/Objective: To quantify the effect on late toxicity of tight margins compared to conservative margins around the gross target volume (GTV), with or without the presence of (elective) nodal field radiation, for radiotherapy for laryngeal carcinoma. Materials and Methods: Two treatment plans, based on conservative (GTV-planning target volume (PTV) = 15 mm and 20mm cranial) and on evidence-based tight margins (GTV-PTV = 8 mm) were calculated for 19 patients with supraglottic cancer. The dose distributions were analyzed and the normal tissue complication rate (NTCP) was calculated for organs at risk (OAR), namely swallowing muscles and submandibular glands. Target structures and OARs were delineated on a planning-CT with a slice thickness of 2 mm. For calculation the NTCP of grade 2 or more swallowing dysfunction we used the model of Jackson et al (53th ASTRO meeting). For NTCP of the submandibular glands the model of Dijkema et al (combined Utrecht/ Michigan data, IJROBPh 2010) was used. Patients were divided in three groups: local radiation only (n=3, group 1); N0, including elective irradiation of level II-IV bilaterally (n=10, group 2); N+, including high dose to the positive nodes (n=6, group 3). Results: Compared to conservative margins, using tight margins resulted in: 1) 50% reduction of the PTV; 2) reduction of the normal tissue complication probability (NTCP) for swallowing muscles and submandibular glands; 3) reduction of the mean dose in all organs at risk (OAR); 4) a mean dose smaller than 60 Gy for all OARs, except for the cartilage structures. Reductions were less in the presence of positive nodes (group 3). For these patients, mean NTCP decreased with 29% for the swallowing muscles and with 15% for the submandibular glands by using tight instead of
4th ICHNO conservative margins. In presence of elective nodal fields only (group 2), a mean NTCP-reduction of respectively 53% and 29% was found. The largest reduction in mean NTCP for swallowing muscles and submandibular glands were seen in group 1, see figure 1 for submandibular glands.
Conclusions: There is a theoretical benefit in realizing evidence based, tight, margins for laryngeal cancer patients independent of nodal volumes. Smaller volumes may be obtained by the use of individualized neck support (PTV), online imaging (smaller margins to compensate for movement), better (validated) imaging (GTV), and smaller margins for possible microscopic extension (CTV). PO-091 NG TUBES OR PROPHYLACTIC GASTROSTOMIES? - IMPACT ON LONG TERM SWALLOWING FUNCTION FOLLOWING CHEMORADIOTHERAPY R. Prestwich1, A. Gilbert1, M. Teo1, G. Williams1, K. Dyker1, M. Sen1 1 St James Institute of Oncology, Clinical Oncology, Leeds, United Kingdom Purpose/Objective: The use of prophylactic gastrostomies, compared with nasogastric tubes as required, has been reported to increase the duration of enteral feeding following radical chemoradiotherapy for head and neck cancers. However, it is uncertain if this has a detrimental effect upon long term swallowing function. The aim was to compare long term swallowing outcomes following chemoradiotherapy for oropharynx cancer according to the strategy of enteral feeding support. Materials and Methods: 104 patients who received concurrent chemoradiotherapy for oropharynx squamous cell carcinoma between January 2007-June 2009 were retrospectively identified. Patients who required therapeutic enteral feeding prior to commencing treatment and/or had persistent or recurrent disease on follow up were excluded from analysis. The MD Anderson Dysphagia Inventory (MDADI) was posted up to twice to the remaining 63 disease free patients. MDADI was scored 0-100 in four domains (emotional, physical, functional and global, with higher scores representing better function). Results: MDADI responses were received from 56/63 (89%) patients. Median follow up was 3.8 years (range 2.8-5.2). 43/56 (77%) and 13/56 (23%) had been managed with a prophylactic gastrostomy and nasogastric (NG) tube as required respectively. MDADI scores according to route of enteral feeding are shown in Table 1. On univariate analysis, no significant correlation was found between MDADI score and age, stage, pre-radiotherapy body mass index, baseline diet, use of induction chemotherapy, number of cycles of concurrent chemotherapy and route of enteral feeding.
S37 damage; our data need to be supported by further investigations. PO-088 ACUTE TOXICITY IN HEAD AND NECK CANCER PATIENTS TREATED WITH CHEMORADIATION/CETUXIMAB ± CONSOLIDATION CETUXIMAB O. Riesterer1, K. Bertogg1, B. Shrestha1, S. Weber1, C. Glanzmann1, G. Studer1 1 University Hospital Zurich, Radiation Oncology, Zurich, Switzerland Purpose/Objective: Cetuximab, an anti-EGFR antibody, is a potent enhancer of tumor response when given concurrently with radiotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). Own preclinical data suggest that cetuximab consolidation after radiotherapy targets residual tumor cells in irradiated tumor bed (Riesterer et al, Radiother Oncol 92(3): 383, 2009). Based on this concept a translational research study was launched at the University Hospital Zurich. Materials and Methods: In this phase II study 60 patients with locoregional advanced HNSCC (stage T3-4 Nx or Tx N2b-c (at least 3 nodes) and/or GTV>70cc are treated with standard chemoradiation (IMRT 70 Gy, cisplatin 40mg/m2 weekly) in combination with concurrent cetuximab (loading dose 400mg/m2, then 250mg/m2 weekly). Thereafter patients are randomized to cetuximab consolidation (500 mg/m2 biweekly for 6 infusions) or no consolidation treatment. Integrated into this study is a translational research project with assessment of tissue, serum and imaging biomarker endpoints. Acute toxicity according to CTCAE version 4.03 was assessed weekly during the concurrent and biweekly during the consolidation phase until 14 weeks after end of radiation. Results: So far 20 patients have been included into the study. Two patients withdrew informed consent because of symptoms associated with acne-like-rash grade 3. In one patient consolidation cetuximab was stopped because of decompensated liver cirrhosis grade 4. 16 patients, who completed treatment, are evaluable for the acute toxicity assessment (male/female=15/1, median age 61 y (48-75)). The median GTV size was 54cc (5-100). The median number of infusions given are: cisplatin: 6 (4-6), concurrent cetuximab: 8 (5-8) and consolidation cetuximab: 6 (1-6). The following grade 3 acute toxicity has been observed: mucositis 50% (8/16), dysphagia 56% (9/16), weight loss 6% (1/16), radiation dermatitis 75% (12/16), acne-like rash 12% (2/16), neutropenia 43%, thrombopenia 6% (1/16), infections 6% (1/16). PEGs were inserted in 56% of patients. Tumor response so far is encouraging with only one histologyconfirmed local tumor persistence in a patient with T3N2c hypopharyngeal cancer. Conclusions: Trimodality treatment with chemoradiation and cetuximab is feasible and does not induce higher acute toxicity than expected with chemoradiation alone. Updated data will be presented at the conference. PO-089 THE SELF-CARE REHABILITATION IN THE PATIENTS WITH HEAD AND NECK CANCER TREATED WITH DEFINITIVE RADIOTHERAPY V. Yurut-Caloglu1, F. Ozdemir2, M. Caloglu1, S. Yavuz3, S. Egrenci1 1 Trakya University Medical Faculty, Radiation Oncology, Edirne, Turkey 2 Medipol University Mega Hospitals Complex, Physiotherapy and Rehabilitation Department, Istanbul, Turkey 3 Trakya University Medical Faculty, Physiotherapy and Rehabilitation Department, Edirne, Turkey Purpose/Objective: The restricted mouth opening (trismus)without temporamandibular joint invasion- is an important late adverse effect of radiotherapy in patients with head and neck cancer. The aim of this study is to determine whether
S38 rehabilitation therapy provides any therapeutic effect on mouth opening in these patients cohort after radiotherapy. Materials and Methods: Fifty-four consecutive patients with squamous cell carcinoma of the head and neck treated with radiotherapy and/or chemotherapy were included in this study. All patients had at least three months since the end of radiotherapy. Mouth opening distance (MOD) ≤35 mm was defined as trismus. MODs were measured twice, once at the beginning of study and once after three months of exercise. Results: Median age was 59 years (range; 31-84). The mean MOD was 37.1 mm (range; 8-62 mm) at the beginning and 38.5 mm (range; 10-62 mm) after physiotherapy (p<0.0001). These values were 30.5 mm (range; 8-35 mm) and 33.4 mm (range; 10-40 mm) in patients with trismus (p<0.0001 respectively); and were 42 mm (range 37-62 mm) and 42.3 mm (range 37-62 mm) in patients without trismus (p=0.009, respectively). The mean MOD were significantly lower in patients who received concurrent chemotherapy (p=0.032) and with higher T stage (p=0.004) at the beginning. Physiotherapy significantly improved the MODs of patients either received concurrent chemotherapy (p<0.0001) or not received (p<0.0001). The mean MOD increased significantly in patients with T1 (p=0.006), T2 (p=0.002), and T4 (p=0.001) tumor stage by physiotherapy but not in patients with T3 (p>0.05). Conclusions: The self rehabilitation method was an effective method for trismus treatment in head and neck cancer patients after definitive radiotherapy. PO-090 SMALLER MARGINS DO MATTER IN RADIOTHERAPY FOR LARYNGEAL CANCER C. Terhaard1, C.A.J.M. Vugts2, M.E.P. Philippens1, N. Kasperts1, F. Pameijer3, C.P.J. Raaijmakers1 1 UMC Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands 2 Institute Verbeeten, Radiation Oncology, Tilburg, The Netherlands 3 UMC Utrecht, Department of Radiology, Utrecht, The Netherlands Purpose/Objective: To quantify the effect on late toxicity of tight margins compared to conservative margins around the gross target volume (GTV), with or without the presence of (elective) nodal field radiation, for radiotherapy for laryngeal carcinoma. Materials and Methods: Two treatment plans, based on conservative (GTV-planning target volume (PTV) = 15 mm and 20mm cranial) and on evidence-based tight margins (GTV-PTV = 8 mm) were calculated for 19 patients with supraglottic cancer. The dose distributions were analyzed and the normal tissue complication rate (NTCP) was calculated for organs at risk (OAR), namely swallowing muscles and submandibular glands. Target structures and OARs were delineated on a planning-CT with a slice thickness of 2 mm. For calculation the NTCP of grade 2 or more swallowing dysfunction we used the model of Jackson et al (53th ASTRO meeting). For NTCP of the submandibular glands the model of Dijkema et al (combined Utrecht/ Michigan data, IJROBPh 2010) was used. Patients were divided in three groups: local radiation only (n=3, group 1); N0, including elective irradiation of level II-IV bilaterally (n=10, group 2); N+, including high dose to the positive nodes (n=6, group 3). Results: Compared to conservative margins, using tight margins resulted in: 1) 50% reduction of the PTV; 2) reduction of the normal tissue complication probability (NTCP) for swallowing muscles and submandibular glands; 3) reduction of the mean dose in all organs at risk (OAR); 4) a mean dose smaller than 60 Gy for all OARs, except for the cartilage structures. Reductions were less in the presence of positive nodes (group 3). For these patients, mean NTCP decreased with 29% for the swallowing muscles and with 15% for the submandibular glands by using tight instead of
4th ICHNO conservative margins. In presence of elective nodal fields only (group 2), a mean NTCP-reduction of respectively 53% and 29% was found. The largest reduction in mean NTCP for swallowing muscles and submandibular glands were seen in group 1, see figure 1 for submandibular glands.
Conclusions: There is a theoretical benefit in realizing evidence based, tight, margins for laryngeal cancer patients independent of nodal volumes. Smaller volumes may be obtained by the use of individualized neck support (PTV), online imaging (smaller margins to compensate for movement), better (validated) imaging (GTV), and smaller margins for possible microscopic extension (CTV). PO-091 NG TUBES OR PROPHYLACTIC GASTROSTOMIES? - IMPACT ON LONG TERM SWALLOWING FUNCTION FOLLOWING CHEMORADIOTHERAPY R. Prestwich1, A. Gilbert1, M. Teo1, G. Williams1, K. Dyker1, M. Sen1 1 St James Institute of Oncology, Clinical Oncology, Leeds, United Kingdom Purpose/Objective: The use of prophylactic gastrostomies, compared with nasogastric tubes as required, has been reported to increase the duration of enteral feeding following radical chemoradiotherapy for head and neck cancers. However, it is uncertain if this has a detrimental effect upon long term swallowing function. The aim was to compare long term swallowing outcomes following chemoradiotherapy for oropharynx cancer according to the strategy of enteral feeding support. Materials and Methods: 104 patients who received concurrent chemoradiotherapy for oropharynx squamous cell carcinoma between January 2007-June 2009 were retrospectively identified. Patients who required therapeutic enteral feeding prior to commencing treatment and/or had persistent or recurrent disease on follow up were excluded from analysis. The MD Anderson Dysphagia Inventory (MDADI) was posted up to twice to the remaining 63 disease free patients. MDADI was scored 0-100 in four domains (emotional, physical, functional and global, with higher scores representing better function). Results: MDADI responses were received from 56/63 (89%) patients. Median follow up was 3.8 years (range 2.8-5.2). 43/56 (77%) and 13/56 (23%) had been managed with a prophylactic gastrostomy and nasogastric (NG) tube as required respectively. MDADI scores according to route of enteral feeding are shown in Table 1. On univariate analysis, no significant correlation was found between MDADI score and age, stage, pre-radiotherapy body mass index, baseline diet, use of induction chemotherapy, number of cycles of concurrent chemotherapy and route of enteral feeding.