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Survival and prognostic factors of nasopharyngeal cancer patients in non-endemic countries: A large multicentric database analysis
abstracts
Annals of Oncology
time employment, Spouse / Financial dependant: Warwickshire Head and Neck Clinic; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi Pasteur; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Honoraria (self), Research grant / Funding (self): AstraZeneca; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Silence Therapeutics. All other authors have declared no conflicts of interest.
1112PD
Efficacy evaluation of optimal patient selection for hypopharyngeal cancer organ preservation therapy using MRI-derived radiomic signature: Bi-institutional propensity score matched analysis
S-M. Lin1, C. Hsu2, Y. Lee3, T-C. Li4, S-H. Kuo5, W. Wang6 Radiation Oncology, Chang Gung Medical Foundation - Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, 2Department of Oncology, National Taiwan University Hostipal, Taipei, Taiwan, 3Mathematics, National Taiwan University, Taipei, Taiwan, 4Radiation Oncology, National Taiwan University Hospital, Taipei, Taiwan, 5 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 6 Institute of Applied Mathematical Sciences, National Taiwan University, Taipei, Taiwan
1
Background: Early loco-regional failure (LRF) after organ preservation therapy (OPT) varies widely for hypopharyngeal squamous cell carcinoma (HPSCC) patients. We aim to develop and validate a MRI-derived radiomic signature RS for the prediction of 1year LRF in HPSCC treated with OPT, and investigate its efficacy between OPT and total laryngectomy (TL) cohort. Methods: A total of 3912 MRI-based radiomic features (RF) of pretreatment tumors were obtained from 370 HPSCC patients, including OPT cohort1 (OPT1; n ¼ 186), OPT cohort2 (OPT2; n ¼ 88), and TL cohort (TLc; n ¼ 96). Variational autoencoder (VAE), trained with symmetric two encoded and decoded layers of neural network was applied to reduce the dimensionality of original RF to 128 VAE-RF. Least absolute shrinkage and selection operator with 10-fold cross validation performs features selection and constructs RS to predict 1-year LRF events in OPT1, which was validated in OPT2 and TLC. Harrell’s C-index was used to evaluate the discriminative ability of RS. Optimal cut-point for dichotomized RS risk category was determined via Youden index. Pair-wise propensity score matching (caliper 0.2) using pre-treatment variables (age, gender, TNM stage) was applied to compare the impact of OPT and TL under different RS risk categories. Results: The RS yielded 1000 times bootstrapping corrected C-index of 0.753, 0.745 and 0.398 in the OPT1, OPT2 and TLC, respectively. Dichotomized risk category using Youden cut-point of RS yielded 1 year LRF predictive accuracy of 71.12%, 70.41%, and 41.74% in OPT1, OPT2 and TLC, respectively. In RS-high risk group, OPT were associated with poor progression-free survival (PFS, HR: 1.752, p ¼ 0.032), while in RS-low risk group, OPT did not deteriorate the PFS (HR: 0.774, p ¼ 0.416). Conclusions: The RS-based model provides a novel to predict 1-year LRF and survival in patients with HPSCC who received OPT. The prediction performance discrepancy of MRI-derived RS in TLC also emphasizes the role of TL in RS-high risk group. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | September 2019
1113PD
Survival and prognostic factors of nasopharyngeal cancer patients in non-endemic countries: A large multicentric database analysis
P. Bossi1, S. Grisanti1, I. Mohamad2, I. Linares Galiana3, E. Ozyar4, P. Franco5, S. Vecchio6, L. Livi7, B. Cirauqui Cirauqui8, M. El-Sherify9, S. Ursino10, A. Argiris11, J. Pan12, C. Wittekindt13, E. D’angelo14, M. Buglione15, M. Airoldi16, R. Mesia Nin17, L.F. Licitra18, E. Orlandi19 1 Medical Oncology Department, Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy, 2Radiation Oncology Department, King Hussein Cancer Centre, Amman, Jordan, 3 Medical Oncology, Institut Catal a d’Oncologia Hospital Duran i Reynals, Barcelona, Spain, 4Radiation Oncology Department, ACIBADEM University, Istanbul, Turkey, 5 Radiation Oncology Department, University of Turin, Turin, Italy, 6Oncology, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy, 7 Radiation Oncology, AOU Careggi - Radioterapia Oncologica, Florence, Italy, 8Medical Oncology Department, Catalan Institute of Oncology (ICO), Badalona, Spain, 9 Radiation Oncologist Department, Kuwait Cancer Control Center Al Sabah Hospital, Shuwaikh, El-Gamalia, Kuwait, 10Radiation Oncology Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, 11Medical Oncology, Hygeia Hospital, Athens, Greece, 12Radiation Oncology Department, Thomas Jefferson University, Philadelphia, PA, USA, 13Otorhinolaryngology, University Hospital Giessen, Giessen, Germany, 14Radiation Oncology Department, Azienda Ospedaliero-Universitaria Modena Policlinico, Modena, Italy, 15Radiation Oncology Department, Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy, 16Medical Oncology, AOU S. Giovanni a Battista - Molinette, Turin, Italy, 17Medical Oncology Department, Institut Catal d’Oncologia, Badalona, Spain, 18Head and Neck Medical Oncology Unit, Istituto 19 Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, Radiation Oncology Department, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy Background: Nasopharyngeal carcinoma (NPC) is a rare cancer in many areas including Europe and Middle East/Mediterranean. Data regarding natural history, prognostic factors and treatment strategies in NPC patients (pts) are derived mostly from studies conducted in endemic regions. Methods: We collected clinical data on consecutive NPC pts treated in non-endemic countries from 2005 to 2016. Main objective of the study was to collect clinical/biological parameters and to correlate them with the outcome, at uni- and multivariate analysis, using the Cox regression model. Results: The database included 1220 pts from 34 Centers. They were mainly male (72%), with ECOG performance status (PS) 0 in 74% of the cases, with advanced stages (stage III 42%, IV 33%), and with a median age of 50 years. Tumoral EBER was assessed in 51% (42% positive); plasmatic EBV DNA was evaluated at baseline in 23% of the pts, with a mean value of 12,434 copies/mL (range 0-824,525). Induction, concurrent and adjuvant chemotherapy (CT), were administered to 45%, 83% and 11% of the pts, respectively. Main RT techniques employed were IMRT (81%) and 3DRT (19%). With a median follow up of 56.5 months, 3- and 5-year overall survival (OS) was 83% and 77%, respectively. Among the 411 pts who relapsed, distant metastases were the pattern of failure in 55%, with bone (49%), lung (31%) and liver (29%) as the most represented sites. At relapse, main treatment approach was CT (45%), surgery (24%), re-RT (9%), or supportive care only (10%). At univariate analysis, prognostic factors favorably correlated with OS were: PS (0-1 vs > 1, p < 0.0001); female sex (p ¼ 0.001); global stage (I-II vs III vs IV, p < 0.0001), T stage (T1-T2 vs T3-T4, p < 0.0001), N stage (N0-N1 vs N2-N3, p ¼ 0.0242), baseline plasmatic EBV > 4000 copies/mL (p ¼ 0.0073). At multivariate analysis, all the variables confirmed their prognostic value. Conclusions: In non-endemic countries, NPC showed survival figures comparable to endemic areas. Stage, PS, gender and plasmatic EBV DNA turned out to be prognostic factors. These data represent the benchmark in non-endemic setting and the referral for building new prospective trials. Legal entity responsible for the study: Fondazione IRCCS Istituto Nazionale Tumori Milano. Funding: Has not received any funding. Disclosure: P. Bossi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Angelini; Advisory / Consultancy: Merck; Advisory / Consultancy: Voluntis. R. Mesia Nin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: Nanobiotix. L.F. Licitra: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Research grant / Funding (institution): EISAI; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Research grant / Funding (institution): Boehringer; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self), Travel / Accommodation / Expenses: Debiopharm; Honoraria (self), Travel / Accommodation / Expenses: Sobi; Honoraria (self): Doxa Pharma srl; Honoraria (self): Nanobiotics; Honoraria (self): GSK; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Exelixis Inc.; Research grant / Funding (institution): Hoffmann-La Roche Ltd.; Research grant / Funding (institution): IRX Therapeutics, Inc.; Research grant / Funding (institution): Medpace INC.; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Stilema, AccMed, Aiocc, Aiom; Honoraria (self): Amgen. All other authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz252 | v451
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz252.005/5578188 by guest on 24 October 2019
Results: 334 patients were randomised to cisplatin (n ¼ 166) or cetuximab (n ¼ 168). EQ-5D-5L utility index scores showed substantially lower mean QoL at the end of treatment for both study arms compared to baseline, before both recovering by 12 months PT. No significant differences between arms were detected at any time point. The difference in cumulative quality-adjusted survival, adjusted for baseline QoL, gender and comorbidities, widened over time and became significant at 6 months PT. By 24 months PT, mean difference was 0.107 QALYs in favour of cisplatin (95% CI: 0.029 to 0.186, p ¼ 0.007), driven by the higher rate of mortality in the cetuximab arm. We found no statistically significant differences in the mean number or cost of hospital inpatient days, day case/outpatient visits, A&E visits, or primary/community care contacts. The cost of cetuximab-based chemoradiotherapy was, however, £7780 (P < 0.001) more expensive. Total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab. Treatment with cetuximab therefore significantly increased total cost per patient by £7547 (95% CI: £6512 to £8582). Conclusions: When added to radiotherapy, cisplatin chemotherapy provided more QALYs and was less costly than cetuximab. Clinical trial identification: NCT01874171. Legal entity responsible for the study: Hisham Mohamed Mehanna. Funding: Cancer Research UK. Disclosure: H. Mehanna: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-
Annals of Oncology
time employment, Spouse / Financial dependant: Warwickshire Head and Neck Clinic; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi Pasteur; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Honoraria (self), Research grant / Funding (self): AstraZeneca; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Silence Therapeutics. All other authors have declared no conflicts of interest.
1112PD
Efficacy evaluation of optimal patient selection for hypopharyngeal cancer organ preservation therapy using MRI-derived radiomic signature: Bi-institutional propensity score matched analysis
S-M. Lin1, C. Hsu2, Y. Lee3, T-C. Li4, S-H. Kuo5, W. Wang6 Radiation Oncology, Chang Gung Medical Foundation - Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, 2Department of Oncology, National Taiwan University Hostipal, Taipei, Taiwan, 3Mathematics, National Taiwan University, Taipei, Taiwan, 4Radiation Oncology, National Taiwan University Hospital, Taipei, Taiwan, 5 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, 6 Institute of Applied Mathematical Sciences, National Taiwan University, Taipei, Taiwan
1
Background: Early loco-regional failure (LRF) after organ preservation therapy (OPT) varies widely for hypopharyngeal squamous cell carcinoma (HPSCC) patients. We aim to develop and validate a MRI-derived radiomic signature RS for the prediction of 1year LRF in HPSCC treated with OPT, and investigate its efficacy between OPT and total laryngectomy (TL) cohort. Methods: A total of 3912 MRI-based radiomic features (RF) of pretreatment tumors were obtained from 370 HPSCC patients, including OPT cohort1 (OPT1; n ¼ 186), OPT cohort2 (OPT2; n ¼ 88), and TL cohort (TLc; n ¼ 96). Variational autoencoder (VAE), trained with symmetric two encoded and decoded layers of neural network was applied to reduce the dimensionality of original RF to 128 VAE-RF. Least absolute shrinkage and selection operator with 10-fold cross validation performs features selection and constructs RS to predict 1-year LRF events in OPT1, which was validated in OPT2 and TLC. Harrell’s C-index was used to evaluate the discriminative ability of RS. Optimal cut-point for dichotomized RS risk category was determined via Youden index. Pair-wise propensity score matching (caliper 0.2) using pre-treatment variables (age, gender, TNM stage) was applied to compare the impact of OPT and TL under different RS risk categories. Results: The RS yielded 1000 times bootstrapping corrected C-index of 0.753, 0.745 and 0.398 in the OPT1, OPT2 and TLC, respectively. Dichotomized risk category using Youden cut-point of RS yielded 1 year LRF predictive accuracy of 71.12%, 70.41%, and 41.74% in OPT1, OPT2 and TLC, respectively. In RS-high risk group, OPT were associated with poor progression-free survival (PFS, HR: 1.752, p ¼ 0.032), while in RS-low risk group, OPT did not deteriorate the PFS (HR: 0.774, p ¼ 0.416). Conclusions: The RS-based model provides a novel to predict 1-year LRF and survival in patients with HPSCC who received OPT. The prediction performance discrepancy of MRI-derived RS in TLC also emphasizes the role of TL in RS-high risk group. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | September 2019
1113PD
Survival and prognostic factors of nasopharyngeal cancer patients in non-endemic countries: A large multicentric database analysis
P. Bossi1, S. Grisanti1, I. Mohamad2, I. Linares Galiana3, E. Ozyar4, P. Franco5, S. Vecchio6, L. Livi7, B. Cirauqui Cirauqui8, M. El-Sherify9, S. Ursino10, A. Argiris11, J. Pan12, C. Wittekindt13, E. D’angelo14, M. Buglione15, M. Airoldi16, R. Mesia Nin17, L.F. Licitra18, E. Orlandi19 1 Medical Oncology Department, Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy, 2Radiation Oncology Department, King Hussein Cancer Centre, Amman, Jordan, 3 Medical Oncology, Institut Catal a d’Oncologia Hospital Duran i Reynals, Barcelona, Spain, 4Radiation Oncology Department, ACIBADEM University, Istanbul, Turkey, 5 Radiation Oncology Department, University of Turin, Turin, Italy, 6Oncology, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy, 7 Radiation Oncology, AOU Careggi - Radioterapia Oncologica, Florence, Italy, 8Medical Oncology Department, Catalan Institute of Oncology (ICO), Badalona, Spain, 9 Radiation Oncologist Department, Kuwait Cancer Control Center Al Sabah Hospital, Shuwaikh, El-Gamalia, Kuwait, 10Radiation Oncology Department, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, 11Medical Oncology, Hygeia Hospital, Athens, Greece, 12Radiation Oncology Department, Thomas Jefferson University, Philadelphia, PA, USA, 13Otorhinolaryngology, University Hospital Giessen, Giessen, Germany, 14Radiation Oncology Department, Azienda Ospedaliero-Universitaria Modena Policlinico, Modena, Italy, 15Radiation Oncology Department, Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy, 16Medical Oncology, AOU S. Giovanni a Battista - Molinette, Turin, Italy, 17Medical Oncology Department, Institut Catal d’Oncologia, Badalona, Spain, 18Head and Neck Medical Oncology Unit, Istituto 19 Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, Radiation Oncology Department, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy Background: Nasopharyngeal carcinoma (NPC) is a rare cancer in many areas including Europe and Middle East/Mediterranean. Data regarding natural history, prognostic factors and treatment strategies in NPC patients (pts) are derived mostly from studies conducted in endemic regions. Methods: We collected clinical data on consecutive NPC pts treated in non-endemic countries from 2005 to 2016. Main objective of the study was to collect clinical/biological parameters and to correlate them with the outcome, at uni- and multivariate analysis, using the Cox regression model. Results: The database included 1220 pts from 34 Centers. They were mainly male (72%), with ECOG performance status (PS) 0 in 74% of the cases, with advanced stages (stage III 42%, IV 33%), and with a median age of 50 years. Tumoral EBER was assessed in 51% (42% positive); plasmatic EBV DNA was evaluated at baseline in 23% of the pts, with a mean value of 12,434 copies/mL (range 0-824,525). Induction, concurrent and adjuvant chemotherapy (CT), were administered to 45%, 83% and 11% of the pts, respectively. Main RT techniques employed were IMRT (81%) and 3DRT (19%). With a median follow up of 56.5 months, 3- and 5-year overall survival (OS) was 83% and 77%, respectively. Among the 411 pts who relapsed, distant metastases were the pattern of failure in 55%, with bone (49%), lung (31%) and liver (29%) as the most represented sites. At relapse, main treatment approach was CT (45%), surgery (24%), re-RT (9%), or supportive care only (10%). At univariate analysis, prognostic factors favorably correlated with OS were: PS (0-1 vs > 1, p < 0.0001); female sex (p ¼ 0.001); global stage (I-II vs III vs IV, p < 0.0001), T stage (T1-T2 vs T3-T4, p < 0.0001), N stage (N0-N1 vs N2-N3, p ¼ 0.0242), baseline plasmatic EBV > 4000 copies/mL (p ¼ 0.0073). At multivariate analysis, all the variables confirmed their prognostic value. Conclusions: In non-endemic countries, NPC showed survival figures comparable to endemic areas. Stage, PS, gender and plasmatic EBV DNA turned out to be prognostic factors. These data represent the benchmark in non-endemic setting and the referral for building new prospective trials. Legal entity responsible for the study: Fondazione IRCCS Istituto Nazionale Tumori Milano. Funding: Has not received any funding. Disclosure: P. Bossi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Angelini; Advisory / Consultancy: Merck; Advisory / Consultancy: Voluntis. R. Mesia Nin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: Nanobiotix. L.F. Licitra: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Research grant / Funding (institution): EISAI; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Research grant / Funding (institution): Boehringer; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self), Travel / Accommodation / Expenses: Debiopharm; Honoraria (self), Travel / Accommodation / Expenses: Sobi; Honoraria (self): Doxa Pharma srl; Honoraria (self): Nanobiotics; Honoraria (self): GSK; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Exelixis Inc.; Research grant / Funding (institution): Hoffmann-La Roche Ltd.; Research grant / Funding (institution): IRX Therapeutics, Inc.; Research grant / Funding (institution): Medpace INC.; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Stilema, AccMed, Aiocc, Aiom; Honoraria (self): Amgen. All other authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz252 | v451
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz252.005/5578188 by guest on 24 October 2019
Results: 334 patients were randomised to cisplatin (n ¼ 166) or cetuximab (n ¼ 168). EQ-5D-5L utility index scores showed substantially lower mean QoL at the end of treatment for both study arms compared to baseline, before both recovering by 12 months PT. No significant differences between arms were detected at any time point. The difference in cumulative quality-adjusted survival, adjusted for baseline QoL, gender and comorbidities, widened over time and became significant at 6 months PT. By 24 months PT, mean difference was 0.107 QALYs in favour of cisplatin (95% CI: 0.029 to 0.186, p ¼ 0.007), driven by the higher rate of mortality in the cetuximab arm. We found no statistically significant differences in the mean number or cost of hospital inpatient days, day case/outpatient visits, A&E visits, or primary/community care contacts. The cost of cetuximab-based chemoradiotherapy was, however, £7780 (P < 0.001) more expensive. Total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab. Treatment with cetuximab therefore significantly increased total cost per patient by £7547 (95% CI: £6512 to £8582). Conclusions: When added to radiotherapy, cisplatin chemotherapy provided more QALYs and was less costly than cetuximab. Clinical trial identification: NCT01874171. Legal entity responsible for the study: Hisham Mohamed Mehanna. Funding: Cancer Research UK. Disclosure: H. Mehanna: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-