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immunotherapy for locally advanced maxillary cancer. Case report
abstracts
Annals of Oncology P2 144
Induction SBRT followed by chemotherapy/immunotherapy for locally advanced maxillary cancer. Case report
Masao Toji1, Shinichiro Miyazaki2 Otorhinolaryngology Department, Shin-yurigaoka General Hospital, 2Radiation Oncology Department, Shin-yurigaoka General Hospital
1
P2 145
Hypopharyngeal cancer patient with autoimmune myositis and myasthenia gravis emerged after nivolumab administration
Masao Toji1, Shinichiro Miyazaki2 Otorhinolaryngology Department, Shin-yurigaoka General Hospital, 2Radiation Oncology Department, Shin-yurigaoka General Hospital
1
Background: The immune checkpoint inhibitor(ICI) was approved for head and neck cancer refractory to cDDP, thereafter promptly its survival benefit had been demonstrated. Synergistic effect by combination of SBRT regarded as in situ vaccination and immunotherapy is theoretically expected, but simultaneously an increase in the incidence of irAE by ICI is also concerned. Case: A 78-year-old man with T4aN2bM0 hypopharyngeal squamous cell carcinoma of posterior wall type underwent SBRT, which resulted in CR. Afterwards bilateral cervical lymph node metastasis and lung metastasis appeared (rT0N2cM1) and were hit by SBRT, but the right upper deep cervical lesion gradually increased. Then chemotherapy (TXT/ CDGP) was performed, which resulted in reduction of pulmonary (MR), but right cervical metastasis was SD, then nivolumab was started. After third course, general fatigue and dysphagia associated with a rise in CK/CKMB appeared. Autoimmune myositis as irAE was suspected and the patient was hospitalized. Mild right ptosis was also observed which was considered at first as Horner symptom since AchR antibody was negative, but tensilon test proved positive, which lead to the diagnosis of autoimmune myositis associated with myasthenia gravis. PSL 1 mg / kg was administrated and gradually decreased every week, then the CK/CKMB value improved remarkably and clinical symptoms were also relieved. The right upper deep neck lesion shrank remarkably on the onset of irAE, but pulmonary metastasis was SD. CR of the neck lesion has persisted to date but the right middle lung field metastatic lesion tended to grow and was submitted to SBRT. Discussion: The onset of autoimmune myositis and myasthenia gravis has the risk of leading to fatal heart failure, thus it is mandatory to immediately discontinue treatment and to cope with, regardless of the anti-tumor effect. Regular CK measurement and careful observation are essential on nivolumab administration.
P2 150
Experience of lenvatinib therapy for patients with differentiated thyroid cancer in our hospital
Keisuke Miwa1,3, Masaru Fukahori1,2, Toshimitsu Tanaka1,2, Sachiko Nagasu1,3, Tomoyuki Ushijima1,2, Kouta Shigetou1,2, Takeharu Ono4, Hirohito Umeno4, Takuji Torimura2, Yoshito Akagi3 1 Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 2Department of Medichine, Division of Gastroenterology, Kurume University, 3Department of Surgery. Kurume University School of Medicine, 4Kurume University School of Medicine Department of Otolaryngology, Head and Neck Surgery. Background It has been shown that lenvatinib is effective in patients with radioactive iodine- (RAI) refractory differentiated thyroid cancer; however, there are few reports of its use in clinical practice.
Volume 30 | Supplement 6 | October 2019
P2 151
Lenvatinib, In Treating Advanced Malignant Thyroid Tumours, Real Life Experience from University Malaya Medical Centre
Yin Keong Teo1, Wan Zamaniah Binti Wan Ishak2 Department of Radiotherapy and Oncology, Hospital Sultan Ismail, Johor Bahru, Johor, Malaysia, 2Clinical Oncology Unit, Faculty of Medicine, University Malaya, Kuala Lumpur
1
Background: Differentiated thyroid cancer (DTC) is the commonest endocrine cancer in Malaysia. Chemotherapy and radiotherapy has limited role in managing radioactive iodine (RAI)-refractory DTC. With the understanding of the molecular profiling of DTC, various novel therapies have been developed. Lenvatinib is a multiple kinase inhibitor (MKI) with promising activities based on the randomized phase III SELECT trial. Our study was to evaluate the safety and efficacy of lenvatinib a real live experience in patients with metastatic RAI-refractory DTC from University Malaya Medical Centre. Methods: RAI-refractory DTC patients with progressive disease and with good performance status (0-2) were screened and treated with lenvatinib at UMMC from November 2014 to April 2017 with Eisai Named Patient Assisted Programme (NPAP) and the data was collected and analysed. Data collection was ended on June 2018. Results: There were 23 patients with a median of 65 years (31-76) were enrolled. The male: female ratio was 1:1. All patients had prior thyroid surgery with history of at least once RAI treatment. Only 2 patients (8.7%) had prior therapy with sorafenib. Commonest sites of metastases were lung and bones. 47% of patients showed positive clinical response and 8.7% showed radiological response and 82.6% has biochemical response. Median overall survival (OS) was not ready to be calculated, and median progression free survival (PFS) was 23.9 months. Common adverse events (AE) observed in all grades were hypertension (87.0%), fatigue (95.7%), proteinuria (69.6%), skin reactions (52.2%) and diarrhoea (43.5%). Almost all cases had dose interruptions and reductions due to AE and it was done within initial 2 months of therapy. 26.7% of patients are still on the treatment. Conclusions: Lenvatinib is a new treatment option with significant clinical benefit for patients with metastatic RAI-refractory DTC. It has significant adverse events but manageable toxicity with dose interruptions.
P2 155
Racial Disparities in Incidence and Mortality Trends of Glioblastoma; A Population-Based Study
Inas A Ruhban1, Mahmad Wafa Khoudeir2, Anas M Saad2, Muneer J Al-Husseini2, Khalid A Jazieh3, Muayad A Alzuabi4, Mohamed M Gad3,5 1 Pathology department, Faculty of Medicine, Damascus University, Damascus, Syria, Egypt, 2Faculty of Medicine, Ain Shams University, Cairo, Egypt, 3Cleveland Clinic Foundation, Ohio, USA, 4Evidence-based Practice Center, Mayo Clinc, Rochester, MN, 5 Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Background: Glioblastoma is one of the most aggressive brain malignancies in adults with limited data evaluating the racial disparities in incidence or mortality. In this study, we aim to study the temporal trends of incidence and mortality and assess ethnic impact on the outcomes. Methods: We used the SEER database to study glioblastoma cases in the US during 1992-2015. Incidence and mortality rates of glioblastoma were calculated by race and were expressed in 100,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software. Results: We reviewed 27,905 glioblastoma patients, of which 1,518 were Asians, 1,471 were blacks, 127 were American Indians, and the others were whites. The incidence of glioblastoma was highest among whites (3.43) when compared to Asians (1.417), and blacks (1.724). Glioblastoma incidence among whites increased significantly over the
doi:10.1093/annonc/mdz343 | vi133
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.069/5583182 by Goteborgs Universitet user on 24 November 2019
Background: We have applied CyberKnife(CK)-based SBRT to hundreds of patients with primary advanced head and neck cancer (AHNC). Thereby although rarely, we experienced emergence of host-tumor interactions suggestive of immunological modulation among high responders such as the abscopal effect or the emergence of autoimmune diseases reminiscent of irAE. There we reasoned that SBRT did not only ablate tumor but exerted as in situ vaccination. Assuming that, it is rational to combine immunotherapy following SBRT. Objectives: Complete cure was obtained in a patient with locally advanced stage IVB maxillary cancer by CK-SBRT with semi-concurrent chemotherapy followed by nivolumab administration. To report clinical consequence. Case report: 68 year-old male patient with T4bN2bM0 maxillary SCC with intra-dural and severe orbital involvement was treated by IRB-approved SBRT-based clinical practice. Hypofrartionated SBRT was started from the main lesion, then for two sites of N2b. Two course of S-1 / TXT / CDGP was started from the second half of irradiation. Residual lesions were confirmed by PETCT two months after the end of chemotherapy, and nibormab administration was started. CR was confirmed at PETCT at the time of the administration 6 months after the start of nivolumab. Results: Facial edema, eczema and systemic urticaria (Grade 2) were transiently observed but improved by antihistamines and topical steroids. CR of all lesions was achieved. To date there are no signs of recurrence at time that 15 month passed after completion of SBRT. Active social and occupational life of the patient has been realized and maintained. Conclusion: Induction SBRT with immediately followed by combination chemotherapy comprised a taxoid and a cisplatin-derivative and subsequent inhibition of PD1/ PDL1 axis for residual lesions is feasible and compatible with the current health security system and might be be a most potent strategy for AHNC.
Purpose We investigated the efficacy, toxicity, and optimal dose of lenvatinib that had been administered for differentiated thyroid cancer in our hospital. Method We examined dose reduction, dose-limiting toxicity (DLT), optimal dose, response rate (RR), and disease control rate (DCR) in 10 patients who had received lenvatinib for differentiated thyroid cancer from January 2016 to December 2018. Results The mean patient age was 70.5 (50-80) years; there were four men and three women, and all had papillary thyroid cancer. Eight patients had received RAI. In all cases, the starting dose of lenvatinib was 24 mg/day; all patients required interruption and dose reduction. DLT was related to arthralgia in one patient, hand-foot syndrome in one, hypertension in one, and proteinuria in seven. The mean optimal dose of lenvatinib was 10.4 mg/day; 14 mg/day in two patients, 10 mg/day in six, and 8 mg/day in two. The mean interval to optimal dose was 2.4 (1.4-4.7) months. The RR was 40% (partial response in four patients and stable disease in six), making the DCR 100%. Seven patients continued receiving lenvatinib therapy. Discussion In the SELECT study, 67.8% of participants receiving lenvatinib required dose reduction; the mean dose was 17.2 mg/day. However, in the present study, dose reduction was required in all 10 patients, the mean optimum dose being 10.4 mg/day. Conclusion We consider that revision of starting doses and guidelines for reducing the dose of lenvatinib for differentiated thyroid cancer may be necessary.
Annals of Oncology P2 144
Induction SBRT followed by chemotherapy/immunotherapy for locally advanced maxillary cancer. Case report
Masao Toji1, Shinichiro Miyazaki2 Otorhinolaryngology Department, Shin-yurigaoka General Hospital, 2Radiation Oncology Department, Shin-yurigaoka General Hospital
1
P2 145
Hypopharyngeal cancer patient with autoimmune myositis and myasthenia gravis emerged after nivolumab administration
Masao Toji1, Shinichiro Miyazaki2 Otorhinolaryngology Department, Shin-yurigaoka General Hospital, 2Radiation Oncology Department, Shin-yurigaoka General Hospital
1
Background: The immune checkpoint inhibitor(ICI) was approved for head and neck cancer refractory to cDDP, thereafter promptly its survival benefit had been demonstrated. Synergistic effect by combination of SBRT regarded as in situ vaccination and immunotherapy is theoretically expected, but simultaneously an increase in the incidence of irAE by ICI is also concerned. Case: A 78-year-old man with T4aN2bM0 hypopharyngeal squamous cell carcinoma of posterior wall type underwent SBRT, which resulted in CR. Afterwards bilateral cervical lymph node metastasis and lung metastasis appeared (rT0N2cM1) and were hit by SBRT, but the right upper deep cervical lesion gradually increased. Then chemotherapy (TXT/ CDGP) was performed, which resulted in reduction of pulmonary (MR), but right cervical metastasis was SD, then nivolumab was started. After third course, general fatigue and dysphagia associated with a rise in CK/CKMB appeared. Autoimmune myositis as irAE was suspected and the patient was hospitalized. Mild right ptosis was also observed which was considered at first as Horner symptom since AchR antibody was negative, but tensilon test proved positive, which lead to the diagnosis of autoimmune myositis associated with myasthenia gravis. PSL 1 mg / kg was administrated and gradually decreased every week, then the CK/CKMB value improved remarkably and clinical symptoms were also relieved. The right upper deep neck lesion shrank remarkably on the onset of irAE, but pulmonary metastasis was SD. CR of the neck lesion has persisted to date but the right middle lung field metastatic lesion tended to grow and was submitted to SBRT. Discussion: The onset of autoimmune myositis and myasthenia gravis has the risk of leading to fatal heart failure, thus it is mandatory to immediately discontinue treatment and to cope with, regardless of the anti-tumor effect. Regular CK measurement and careful observation are essential on nivolumab administration.
P2 150
Experience of lenvatinib therapy for patients with differentiated thyroid cancer in our hospital
Keisuke Miwa1,3, Masaru Fukahori1,2, Toshimitsu Tanaka1,2, Sachiko Nagasu1,3, Tomoyuki Ushijima1,2, Kouta Shigetou1,2, Takeharu Ono4, Hirohito Umeno4, Takuji Torimura2, Yoshito Akagi3 1 Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 2Department of Medichine, Division of Gastroenterology, Kurume University, 3Department of Surgery. Kurume University School of Medicine, 4Kurume University School of Medicine Department of Otolaryngology, Head and Neck Surgery. Background It has been shown that lenvatinib is effective in patients with radioactive iodine- (RAI) refractory differentiated thyroid cancer; however, there are few reports of its use in clinical practice.
Volume 30 | Supplement 6 | October 2019
P2 151
Lenvatinib, In Treating Advanced Malignant Thyroid Tumours, Real Life Experience from University Malaya Medical Centre
Yin Keong Teo1, Wan Zamaniah Binti Wan Ishak2 Department of Radiotherapy and Oncology, Hospital Sultan Ismail, Johor Bahru, Johor, Malaysia, 2Clinical Oncology Unit, Faculty of Medicine, University Malaya, Kuala Lumpur
1
Background: Differentiated thyroid cancer (DTC) is the commonest endocrine cancer in Malaysia. Chemotherapy and radiotherapy has limited role in managing radioactive iodine (RAI)-refractory DTC. With the understanding of the molecular profiling of DTC, various novel therapies have been developed. Lenvatinib is a multiple kinase inhibitor (MKI) with promising activities based on the randomized phase III SELECT trial. Our study was to evaluate the safety and efficacy of lenvatinib a real live experience in patients with metastatic RAI-refractory DTC from University Malaya Medical Centre. Methods: RAI-refractory DTC patients with progressive disease and with good performance status (0-2) were screened and treated with lenvatinib at UMMC from November 2014 to April 2017 with Eisai Named Patient Assisted Programme (NPAP) and the data was collected and analysed. Data collection was ended on June 2018. Results: There were 23 patients with a median of 65 years (31-76) were enrolled. The male: female ratio was 1:1. All patients had prior thyroid surgery with history of at least once RAI treatment. Only 2 patients (8.7%) had prior therapy with sorafenib. Commonest sites of metastases were lung and bones. 47% of patients showed positive clinical response and 8.7% showed radiological response and 82.6% has biochemical response. Median overall survival (OS) was not ready to be calculated, and median progression free survival (PFS) was 23.9 months. Common adverse events (AE) observed in all grades were hypertension (87.0%), fatigue (95.7%), proteinuria (69.6%), skin reactions (52.2%) and diarrhoea (43.5%). Almost all cases had dose interruptions and reductions due to AE and it was done within initial 2 months of therapy. 26.7% of patients are still on the treatment. Conclusions: Lenvatinib is a new treatment option with significant clinical benefit for patients with metastatic RAI-refractory DTC. It has significant adverse events but manageable toxicity with dose interruptions.
P2 155
Racial Disparities in Incidence and Mortality Trends of Glioblastoma; A Population-Based Study
Inas A Ruhban1, Mahmad Wafa Khoudeir2, Anas M Saad2, Muneer J Al-Husseini2, Khalid A Jazieh3, Muayad A Alzuabi4, Mohamed M Gad3,5 1 Pathology department, Faculty of Medicine, Damascus University, Damascus, Syria, Egypt, 2Faculty of Medicine, Ain Shams University, Cairo, Egypt, 3Cleveland Clinic Foundation, Ohio, USA, 4Evidence-based Practice Center, Mayo Clinc, Rochester, MN, 5 Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Background: Glioblastoma is one of the most aggressive brain malignancies in adults with limited data evaluating the racial disparities in incidence or mortality. In this study, we aim to study the temporal trends of incidence and mortality and assess ethnic impact on the outcomes. Methods: We used the SEER database to study glioblastoma cases in the US during 1992-2015. Incidence and mortality rates of glioblastoma were calculated by race and were expressed in 100,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software. Results: We reviewed 27,905 glioblastoma patients, of which 1,518 were Asians, 1,471 were blacks, 127 were American Indians, and the others were whites. The incidence of glioblastoma was highest among whites (3.43) when compared to Asians (1.417), and blacks (1.724). Glioblastoma incidence among whites increased significantly over the
doi:10.1093/annonc/mdz343 | vi133
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.069/5583182 by Goteborgs Universitet user on 24 November 2019
Background: We have applied CyberKnife(CK)-based SBRT to hundreds of patients with primary advanced head and neck cancer (AHNC). Thereby although rarely, we experienced emergence of host-tumor interactions suggestive of immunological modulation among high responders such as the abscopal effect or the emergence of autoimmune diseases reminiscent of irAE. There we reasoned that SBRT did not only ablate tumor but exerted as in situ vaccination. Assuming that, it is rational to combine immunotherapy following SBRT. Objectives: Complete cure was obtained in a patient with locally advanced stage IVB maxillary cancer by CK-SBRT with semi-concurrent chemotherapy followed by nivolumab administration. To report clinical consequence. Case report: 68 year-old male patient with T4bN2bM0 maxillary SCC with intra-dural and severe orbital involvement was treated by IRB-approved SBRT-based clinical practice. Hypofrartionated SBRT was started from the main lesion, then for two sites of N2b. Two course of S-1 / TXT / CDGP was started from the second half of irradiation. Residual lesions were confirmed by PETCT two months after the end of chemotherapy, and nibormab administration was started. CR was confirmed at PETCT at the time of the administration 6 months after the start of nivolumab. Results: Facial edema, eczema and systemic urticaria (Grade 2) were transiently observed but improved by antihistamines and topical steroids. CR of all lesions was achieved. To date there are no signs of recurrence at time that 15 month passed after completion of SBRT. Active social and occupational life of the patient has been realized and maintained. Conclusion: Induction SBRT with immediately followed by combination chemotherapy comprised a taxoid and a cisplatin-derivative and subsequent inhibition of PD1/ PDL1 axis for residual lesions is feasible and compatible with the current health security system and might be be a most potent strategy for AHNC.
Purpose We investigated the efficacy, toxicity, and optimal dose of lenvatinib that had been administered for differentiated thyroid cancer in our hospital. Method We examined dose reduction, dose-limiting toxicity (DLT), optimal dose, response rate (RR), and disease control rate (DCR) in 10 patients who had received lenvatinib for differentiated thyroid cancer from January 2016 to December 2018. Results The mean patient age was 70.5 (50-80) years; there were four men and three women, and all had papillary thyroid cancer. Eight patients had received RAI. In all cases, the starting dose of lenvatinib was 24 mg/day; all patients required interruption and dose reduction. DLT was related to arthralgia in one patient, hand-foot syndrome in one, hypertension in one, and proteinuria in seven. The mean optimal dose of lenvatinib was 10.4 mg/day; 14 mg/day in two patients, 10 mg/day in six, and 8 mg/day in two. The mean interval to optimal dose was 2.4 (1.4-4.7) months. The RR was 40% (partial response in four patients and stable disease in six), making the DCR 100%. Seven patients continued receiving lenvatinib therapy. Discussion In the SELECT study, 67.8% of participants receiving lenvatinib required dose reduction; the mean dose was 17.2 mg/day. However, in the present study, dose reduction was required in all 10 patients, the mean optimum dose being 10.4 mg/day. Conclusion We consider that revision of starting doses and guidelines for reducing the dose of lenvatinib for differentiated thyroid cancer may be necessary.