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PO-092: Salivary Cytokine Levels and Mucositis in Head and Neck Cancer Patients Treated with Chemoradiotherapy.
4th ICHNO
S39
Table 1: MDADI results according to route of enteral feeding MDADI
Group Gastrostomy mean score (SD)
Group NG P value mean score (SD)
Emotional Physical Functional Global
52.4 (17.7) 57.6 (17.8) 65.5 (22.2) 57.8 (26.5)
46.2 (19.9) 54.2 (19.8) 56.6 (22.7) 53.8 (29.9)
0.519 0.685 0.815 0.318
Conclusions : The choice of either a prophylactic gastrostomy or a NG tube as required does not appear to influence long term swallowing outcomes. PO-092 SALIVARY CYTOKINE LEVELS AND MUCOSITIS IN HEAD AND NECK CANCER PATIENTS TREATED WITH CHEMORADIOTHERAPY. P. Bossi1, P. Filipazzi2, C. Resteghini1, R. Miceli3, L. Rivoltini2, M. Rodolfo2, A. Cova2, P. Squarcina2, E. Orlandi4, L. Licitra1 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology, Milan, Italy 2 Fondazione IRCCS Istituto Nazionale dei Tumori, Immunotherapy of Human Tumors, Milan, Italy 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Biometry and Bioinformatics, Milan, Italy 4 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiation Oncology, Milan, Italy Purpose/Objective: Mucositis is a common complication of chemoradiotherapy (CTRT) for head and neck cancer (HNC), with a recognized balance between pro- and antiinflammation serum cytokines. Due to lack of data about the role of salivary cytokines, we performed a prospective observational study analysing their impact in influencing toxicity severity. Materials and Methods: Fifty-five consecutive stage III (22%) and IV (78%) HNC patients (pts) were treated with radiotherapy (64-70 Gy) plus cisplatin (n=48), carboplatin (n=6) or cetuximab (n=1). Primary tumor site was oral cavity (18%), oropharynx (45%), nasopharynx (27%), larynx or hypopharynx (10%). Unstimulated saliva samples were collected according to standardized protocols before CTRT, during (3rd, 5th and 7th weeks) and two weeks after; concomitantly, mucositis grade (WHO classification), weight loss and need for feeding tube were evaluated. The salivary levels of 13 different cytokines (IFNγ, IL1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNFα, TNFβ, osteopontin, VEGFα) were analysed both in pts and in healthy donors (HD, n=15) by optimized bead-based multiplex immunoassay. Basal cytokine values, the cytokine change during treatment (as the difference between the mean of individual values and the baseline value) and their value at the end of the 3rd week of treatment were associated with toxicity parameters. The Wilcoxon rank sum test and the Kruskal Wallis test were used for between-groups comparisons. Results: At baseline, no difference in cytokine levels was observed in pts as compared with HD, except for IL8. Baseline cytokine salivary levels in pts were not predictive of treatment-induced mucosal toxicity. A significant and progressive increase of IL1β, IL6, IL8, TNFα and IL10 levels was observed during treatment, with high levels persisting two weeks after treatment for all cytokines but IL1β, while osteopontin level showed a progressive decrease during the timeframe. A significant association was shown only between IL1β (p=0.002), IL6 (p<0.001) and TNFα (p=0.001) increase and the development of G3/4 mucositis; IL6 increase was also significantly associated with feeding tube need. Interestingly, pts developing G3/4 mucositis during treatment had significantly higher levels of IL1β, IL6 and TNFα at the 3rd week compared with pts with mucositis grade <3. Conclusions: Salivary IL1β, IL6, IL8, TNFα increase during
CTRT seems to be directly associated with mucosal toxicity. High IL1β, IL6, and TNFα at the 3rd week are predictive of greater mucositis development. Cytokines may represent a potential new target for preventive and/or therapeutic intervention. PO-093 THE TOLERANCE OF TPF FOLLOWED BY RTC IN ADVANCED H&N CANCER PATIENTS - SINGLE-INSTITUTION RETROSPECTIVE ANALYSIS E. Sierko1, D. Hempel1, P. Skalij1, M.Z. Wojtukiewicz1 1 Medical University, Department of Oncology, Bialystok, Poland Purpose/Objective: Radiochemotherapy (RCT) is a treatment of choice for advanced head and neck cancer (H&NC) patients (pts). However, in selected cases (e.g. N2-3) the induction chemotherapy (ICT) is recommended. Preselected pts recruited to the phase III clinical trials differs from population treated in everyday clinical practice. The aim of the study was to analyze safety and compliance of docetaxel, cisplatin, 5-fluorouracyl (TPF) – based ICT followed by 3-D conformal or IMRT radiotherapy (RT) in combination with CT or alone for inoperable H&NC pts. Materials and Methods: 39 pts (35 males and 4 females), mean age 56,2 yrs (range, 38-70 yrs), with diagnosis of H&NC were treated with TPF-based ICT followed by radical RT +/platinum – based CT. The clinical stage of the disease was following: CSII – 1 patient, CSIII – 3 pts and CS IV – 35 pts. The primary tumor was located in the oral cavity – 14 pts, oropharynx – 10 pts, laryngopharynx – 7 pts, larynx – 3 pts, nasopharynx – 2 pts and maxillary sinus– 3 pts. Performance status acc. to WHO was 0 in 54% pts, 1 – in 41% and 2 - in5%. Sixteen patients suffered from co-morbidities (arterial hypertension - 8pts, tuberculosis - 3, diabetes - 4, alcoholism - 4, COPD - 2, ischemic heart disease - 1, cardiomyopathy - 1, renal insufficiency - 1). Prior to the treatment, the mean LV EF was 61%. 6 MVX-ray and 9 and 12 MeV beam electron RT in conventional fractionation was delivered using megavoltage equipment. The mean RT dose of 68.7 Gy (range, 66-72 Gy) was administered in the mean of 47,2 days. Results: Thirty-five (92%) pts finished ICT: 29/39 (74%) pts received 3 courses, whereas 7/39 (18%) pts were administered only 2 courses of TPF due to adverse events. Of note, two pts died following 1st course of ICT and another one – after completion of 2nd course of ICT (in total 9% of the patients). 34/39 pts received full dose of planned CT, while reduction of CT doses were necessary in 3 pts and complete change of CT protocol was required in 2 pts. The mean hemoglobin level prior to ICT was 14.1 g/dl, prior to RTC or RT 11.8 g/dl and after completed treatment – 10.7g/dl. G4 neutropenia occurred in 1 patient. One patient was diagnosed myocardial infarction. 17 pts suffered from G1-2 adverse events during ICT such as: pneumonitis, otitis, phlebitis, mental disorders, abdominal pain, vomits, diarrhea, stroke, renal and hepatic insufficiency, hematological toxicity. After ICT - RR was revealed in 81% pts, namely – CR in 3 pts and PR - 27 (73%) pts. Progression of the disease after induction TPF was observed in 2 pts. Only 22/36 pts (61%) received subsequent RTC. Conclusions: The TPF-based induction chemotherapy is usually well tolerated but may cause serious adverse effects, necessitating dose reduction or premature treatment cessation (especially radical RTC). Further studies are needed to select the group of the pts, who will benefit the most from the combined treatment. PO-094 THE IMPACT OF TOXICITY DURING RADIOCHEMOTHERAPY WITH CETUXIMAB OR CISPLATIN IN OROPHARYNGEAL CANCER R. Autorino1, N. Dinapoli1, G.R. D'Agostino1, G. Mantini1, C. Parrilla2, J. Galli2, F. Bussu2, V. Valentini1, G. Paludetti2, F. Miccichè1
S39
Table 1: MDADI results according to route of enteral feeding MDADI
Group Gastrostomy mean score (SD)
Group NG P value mean score (SD)
Emotional Physical Functional Global
52.4 (17.7) 57.6 (17.8) 65.5 (22.2) 57.8 (26.5)
46.2 (19.9) 54.2 (19.8) 56.6 (22.7) 53.8 (29.9)
0.519 0.685 0.815 0.318
Conclusions : The choice of either a prophylactic gastrostomy or a NG tube as required does not appear to influence long term swallowing outcomes. PO-092 SALIVARY CYTOKINE LEVELS AND MUCOSITIS IN HEAD AND NECK CANCER PATIENTS TREATED WITH CHEMORADIOTHERAPY. P. Bossi1, P. Filipazzi2, C. Resteghini1, R. Miceli3, L. Rivoltini2, M. Rodolfo2, A. Cova2, P. Squarcina2, E. Orlandi4, L. Licitra1 1 Fondazione IRCCS Istituto Nazionale dei Tumori, Medical Oncology, Milan, Italy 2 Fondazione IRCCS Istituto Nazionale dei Tumori, Immunotherapy of Human Tumors, Milan, Italy 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Biometry and Bioinformatics, Milan, Italy 4 Fondazione IRCCS Istituto Nazionale dei Tumori, Radiation Oncology, Milan, Italy Purpose/Objective: Mucositis is a common complication of chemoradiotherapy (CTRT) for head and neck cancer (HNC), with a recognized balance between pro- and antiinflammation serum cytokines. Due to lack of data about the role of salivary cytokines, we performed a prospective observational study analysing their impact in influencing toxicity severity. Materials and Methods: Fifty-five consecutive stage III (22%) and IV (78%) HNC patients (pts) were treated with radiotherapy (64-70 Gy) plus cisplatin (n=48), carboplatin (n=6) or cetuximab (n=1). Primary tumor site was oral cavity (18%), oropharynx (45%), nasopharynx (27%), larynx or hypopharynx (10%). Unstimulated saliva samples were collected according to standardized protocols before CTRT, during (3rd, 5th and 7th weeks) and two weeks after; concomitantly, mucositis grade (WHO classification), weight loss and need for feeding tube were evaluated. The salivary levels of 13 different cytokines (IFNγ, IL1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNFα, TNFβ, osteopontin, VEGFα) were analysed both in pts and in healthy donors (HD, n=15) by optimized bead-based multiplex immunoassay. Basal cytokine values, the cytokine change during treatment (as the difference between the mean of individual values and the baseline value) and their value at the end of the 3rd week of treatment were associated with toxicity parameters. The Wilcoxon rank sum test and the Kruskal Wallis test were used for between-groups comparisons. Results: At baseline, no difference in cytokine levels was observed in pts as compared with HD, except for IL8. Baseline cytokine salivary levels in pts were not predictive of treatment-induced mucosal toxicity. A significant and progressive increase of IL1β, IL6, IL8, TNFα and IL10 levels was observed during treatment, with high levels persisting two weeks after treatment for all cytokines but IL1β, while osteopontin level showed a progressive decrease during the timeframe. A significant association was shown only between IL1β (p=0.002), IL6 (p<0.001) and TNFα (p=0.001) increase and the development of G3/4 mucositis; IL6 increase was also significantly associated with feeding tube need. Interestingly, pts developing G3/4 mucositis during treatment had significantly higher levels of IL1β, IL6 and TNFα at the 3rd week compared with pts with mucositis grade <3. Conclusions: Salivary IL1β, IL6, IL8, TNFα increase during
CTRT seems to be directly associated with mucosal toxicity. High IL1β, IL6, and TNFα at the 3rd week are predictive of greater mucositis development. Cytokines may represent a potential new target for preventive and/or therapeutic intervention. PO-093 THE TOLERANCE OF TPF FOLLOWED BY RTC IN ADVANCED H&N CANCER PATIENTS - SINGLE-INSTITUTION RETROSPECTIVE ANALYSIS E. Sierko1, D. Hempel1, P. Skalij1, M.Z. Wojtukiewicz1 1 Medical University, Department of Oncology, Bialystok, Poland Purpose/Objective: Radiochemotherapy (RCT) is a treatment of choice for advanced head and neck cancer (H&NC) patients (pts). However, in selected cases (e.g. N2-3) the induction chemotherapy (ICT) is recommended. Preselected pts recruited to the phase III clinical trials differs from population treated in everyday clinical practice. The aim of the study was to analyze safety and compliance of docetaxel, cisplatin, 5-fluorouracyl (TPF) – based ICT followed by 3-D conformal or IMRT radiotherapy (RT) in combination with CT or alone for inoperable H&NC pts. Materials and Methods: 39 pts (35 males and 4 females), mean age 56,2 yrs (range, 38-70 yrs), with diagnosis of H&NC were treated with TPF-based ICT followed by radical RT +/platinum – based CT. The clinical stage of the disease was following: CSII – 1 patient, CSIII – 3 pts and CS IV – 35 pts. The primary tumor was located in the oral cavity – 14 pts, oropharynx – 10 pts, laryngopharynx – 7 pts, larynx – 3 pts, nasopharynx – 2 pts and maxillary sinus– 3 pts. Performance status acc. to WHO was 0 in 54% pts, 1 – in 41% and 2 - in5%. Sixteen patients suffered from co-morbidities (arterial hypertension - 8pts, tuberculosis - 3, diabetes - 4, alcoholism - 4, COPD - 2, ischemic heart disease - 1, cardiomyopathy - 1, renal insufficiency - 1). Prior to the treatment, the mean LV EF was 61%. 6 MVX-ray and 9 and 12 MeV beam electron RT in conventional fractionation was delivered using megavoltage equipment. The mean RT dose of 68.7 Gy (range, 66-72 Gy) was administered in the mean of 47,2 days. Results: Thirty-five (92%) pts finished ICT: 29/39 (74%) pts received 3 courses, whereas 7/39 (18%) pts were administered only 2 courses of TPF due to adverse events. Of note, two pts died following 1st course of ICT and another one – after completion of 2nd course of ICT (in total 9% of the patients). 34/39 pts received full dose of planned CT, while reduction of CT doses were necessary in 3 pts and complete change of CT protocol was required in 2 pts. The mean hemoglobin level prior to ICT was 14.1 g/dl, prior to RTC or RT 11.8 g/dl and after completed treatment – 10.7g/dl. G4 neutropenia occurred in 1 patient. One patient was diagnosed myocardial infarction. 17 pts suffered from G1-2 adverse events during ICT such as: pneumonitis, otitis, phlebitis, mental disorders, abdominal pain, vomits, diarrhea, stroke, renal and hepatic insufficiency, hematological toxicity. After ICT - RR was revealed in 81% pts, namely – CR in 3 pts and PR - 27 (73%) pts. Progression of the disease after induction TPF was observed in 2 pts. Only 22/36 pts (61%) received subsequent RTC. Conclusions: The TPF-based induction chemotherapy is usually well tolerated but may cause serious adverse effects, necessitating dose reduction or premature treatment cessation (especially radical RTC). Further studies are needed to select the group of the pts, who will benefit the most from the combined treatment. PO-094 THE IMPACT OF TOXICITY DURING RADIOCHEMOTHERAPY WITH CETUXIMAB OR CISPLATIN IN OROPHARYNGEAL CANCER R. Autorino1, N. Dinapoli1, G.R. D'Agostino1, G. Mantini1, C. Parrilla2, J. Galli2, F. Bussu2, V. Valentini1, G. Paludetti2, F. Miccichè1