Definitive carbon ion radiotherapy for tracheobronchial adenoid cystic carcinoma: a preliminary report

Abstract Background Tracheobronchial adenoid cystic carcinoma (TACC) is a rare tumour. About one-third of patients miss their chance of surgery or complete resection as it is mostly detected in the advanced stage; hence, photon radiotherapy (RT) is used. However, the outcomes of photon RT remain unsatisfactory. Carbon ion radiotherapy (CIRT) is thought to improve the therapeutic gain ratio; however, the outcomes of CIRT in TACC are unclear. Therefore, we aimed to assess the effects and toxicities of CIRT in patients with TACC. Methods The inclusion criteria were as follows: 1) age 18–80 years; 2) Eastern Cooperative Oncology Group Performance Status 0–2; 3) histologically confirmed TACC; 4) stage III–IV disease; 5) visible primary tumour; and 6) no previous RT history. The planned prescription doses of CIRT were 66–72.6 GyE/22–23 fractions. The rates of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Treatment-induced toxicities and tumour response were scored according to the Common Terminology Criteria for Adverse Events and Response Evaluation Criteria in Solid Tumors, respectively. Results Eighteen patients with a median age of 48 (range 30–73) years were enrolled. The median follow-up time was 20.7 (range 5.8–44.1) months. The overall response rate was 88.2%. Five patients developed lung metastasis after 12.2–41.0 months and one of them experienced local recurrence at 31.9 months after CIRT. The rates of 2-year OS, LC, and PFS were 100, 100, and 61.4%, respectively. Except for one patient who experienced grade 4 tracheal stenosis, which was relieved after stent implantation, no other ≥3 grade toxicities were observed. Conclusions CIRT might be safe and effective in the management of TACC based on a short observation period. Further studies with more cases and longer observation are warranted.

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EP-1189 Adenoid Cystic Carcinoma Of The Head And Neck Treated With Carbon Ion Radiotherapy At CNAO

Radiotherapy and Oncology ◽

10.1016/s0167-8140(19)31609-3 ◽

2019 ◽

Vol 133 ◽

pp. S659

Author(s):

M. Bonora ◽

B. Vischioni ◽

D. Caivano ◽

A. Hasegawa ◽

V. Vitolo ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Carbon Ion Radiotherapy ◽

Carbon Ion ◽

Adenoid Cystic

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Carbon Ion Radiotherapy for Adenoid Cystic Carcinoma of the Head and Neck

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2011.06.157 ◽

2011 ◽

Vol 81 (2) ◽

pp. S77-S78

Author(s):

A. Hasegawa ◽

M. Koto ◽

R. Takagi ◽

T. Morikawa ◽

T. Kamada ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Carbon Ion Radiotherapy ◽

Carbon Ion ◽

Adenoid Cystic

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Imatinib Mesylate in Patients With Adenoid Cystic Cancers of the Salivary Glands Expressing c-kit: A Princess Margaret Hospital Phase II Consortium Study

Journal of Clinical Oncology ◽

10.1200/jco.2005.06.125 ◽

2005 ◽

Vol 23 (3) ◽

pp. 585-590 ◽

Cited By ~ 199

Author(s):

Sébastien J. Hotte ◽

Eric W. Winquist ◽

Elizabeth Lamont ◽

Mary MacKenzie ◽

Everett Vokes ◽

...

Keyword(s):

Phase Ii ◽

Tyrosine Kinases ◽

Group Performance ◽

Lung Metastases ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Evaluation Criteria ◽

Growth Factor Receptor ◽

Adenoid Cystic ◽

Best Response

Purpose This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. A high level of c-kit expression has been identified in more than 90% of ACCs. Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases. Patients and Methods In a single-arm, two-stage, phase II clinical trial, adult patients with unresectable or metastatic ACC measurable by Response Evaluation Criteria in Solid Tumors Group criteria and expressing c-kit by immunohistochemistry were treated with imatinib 400 mg orally bid. Response was assessed every 8 weeks. Results Sixteen patients have been enrolled onto the study; 10 were female. Median age was 47 years (range, 31 to 69 years). Median Eastern Cooperative Oncology Group performance status was 1 (range, 0 to 2). Fourteen patients had lung metastases, 14 had prior radiotherapy, and six had prior chemotherapy. Toxicities occurring in at least 50% of patients included fatigue, nausea, vomiting, diarrhea, anorexia, edema, dyspnea, and/or headache, usually of mild to moderate severity. In 15 patients assessable for response, no objective responses have been observed. Nine patients had stable disease as best response. Six patients had progressive disease after two cycles. Conclusion Because of the lack of activity, the study has been stopped after the first stage and additional evaluation of imatinib in this population is not warranted. Overexpression of wild-type c-kit was not sufficient for clinical benefit from imatinib in ACC. Accrual to this study was rapid for a relatively rare cancer, encouraging additional efforts to identify more effective systemic therapy for these patients.

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Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base

Head & Neck ◽

10.1002/hed.24397 ◽

2016 ◽

Vol 38 (S1) ◽

pp. E2122-E2126 ◽

Cited By ~ 10

Author(s):

Masashi Koto ◽

Azusa Hasegawa ◽

Ryo Takagi ◽

Hiroaki Ikawa ◽

Kensuke Naganawa ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Locally Advanced ◽

Tongue Base ◽

Carbon Ion Radiotherapy ◽

Safety And Efficacy ◽

Carbon Ion ◽

Adenoid Cystic ◽

Carcinoma Of The Tongue

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TWO CASES OF MAXILLARY OSTEONECROSIS AFTER CARBON ION RADIOTHERAPY AGAINST ADENOID CYSTIC CARCINOMA

10.26226/morressier.578e3b4ad462b802923819ff ◽

2016 ◽

Author(s):

Tomohiro Hamakawa

Keyword(s):

Adenoid Cystic Carcinoma ◽

Carbon Ion Radiotherapy ◽

Carbon Ion ◽

Adenoid Cystic

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A phase II trial of PS-341 (bortezomib) followed by the addition of doxorubicin at progression in incurable adenoid cystic carcinoma of the head and neck: An Eastern Cooperative Oncology Group study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.5573 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 5573-5573 ◽

Cited By ~ 11

Author(s):

A. Argiris ◽

M. A. Goldwasser ◽

B. Burtness ◽

R. Deconti ◽

R. Axelrod ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Performance Status ◽

Single Agent ◽

Eastern Cooperative Oncology Group ◽

Response To Therapy ◽

26S Proteasome ◽

Ecog Performance Status ◽

Eligibility Criteria ◽

Adenoid Cystic ◽

Ubiquitin Proteasome

5573 Background: Adenoid cystic carcinoma (ACC) is usually resistant to chemotherapy. Bortezomib (B) is a highly selective inhibitor of the 26S proteasome which is central for the ubiquitin-proteasome degradation pathway. Inhibition of NF-κB activity achieved by B may be important for inhibition of the growth of ACC. Preclinical studies have shown synergy between B and doxorubicin (D). Methods: Eligibility criteria included incurable ACC, any number of prior therapies but without an anthracycline, unidimensionally measurable disease, ECOG performance status 0–2, ejection fraction within normal limits (WNL), absolute neutrophil count >1500/μL, platelets >100,000/μL, and total bilirubin WNL. Patients (pts) with stable disease (SD) for 9 months or more were excluded. Pts received B 1.3 mg/m2 IV push on days 1,4,8, and 11, every 21 days, until progression. Doxorubicin 20 mg/m2 IV on days 1 and 8 was added at the time of progression. Response assessment was performed after every 2 cycles using RECIST. Immunohistochemistry for biomarkers affected by the ubiquitin-proteasome pathway on baseline tumor and measurement of serum inflammatory and angiogenic cytokines before and in response to therapy were performed. Results: 25 pts were enrolled; 18 were females; median age was 56 years (26–73); distant metastatic sites: lung (21), liver (4), bone (2). Best response to single-agent B: 16 pts (64%) had SD, 7 progressed, and 2 were unevaluable (1 with symptomatic deterioration). The median progression-free survival was 8.5 months. In 4 evaluable pts who received B plus D, 1 partial response and 2 SD were observed. 1 pt died 7 months after starting treatment without documented progression. Worst grade (G) 3/4 toxicities with B alone in 22 evaluable pts were: G3 neutropenia 5%, G4 neutropenia 5%, G3 thrombocytopenia 5%, G3 sensory neuropathy 14%; G3 generalized weakness 5%, G3 fatigue 9%, G3 anorexia 5%, G3 diarrhea 5%, G3 hyponatremia 5%, G3 dyspnea 5%. Conclusions: B was well tolerated and resulted in disease stabilization in a high percentage of pts but no objective responses. Updated response data with the addition of D will be available. No significant financial relationships to disclose.

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OC-0377: Carbon ion radiotherapy for adenoid cystic carcinoma of the head and neck

Radiotherapy and Oncology ◽

10.1016/s0167-8140(15)30482-5 ◽

2014 ◽

Vol 111 ◽

pp. S145-S146

Author(s):

A. Hasegawa ◽

M. Koto ◽

R. Takagi ◽

H. Ikawa ◽

H. Tsuji ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Carbon Ion Radiotherapy ◽

Carbon Ion ◽

Adenoid Cystic

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In Silico Feasibility Study of Carbon Ion Radiotherapy With Simultaneous Integrated Boost for Head and Neck Adenoid Cystic Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.772580 ◽

2021 ◽

Vol 11 ◽

Author(s):

Edoardo Mastella ◽

Silvia Molinelli ◽

Giuseppe Magro ◽

Stefania Russo ◽

Maria Bonora ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Simultaneous Integrated Boost ◽

Carbon Ion Radiotherapy ◽

Dose Distributions ◽

Carbon Ion ◽

Adenoid Cystic ◽

Sequential Boost ◽

Integrated Boost ◽

Dose Levels

PurposeIn carbon ion radiotherapy (CIRT), a simultaneous integrated boost (SIB) approach has not been fully exploited so far. The feasibility of a CIRT-SIB strategy for head and neck adenoid cystic carcinoma (ACC) patients was investigated in order to improve treatment planning dose distributions.Methods and MaterialsCIRT plans of 10 ACC patients treated at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) with sequential boost (SEQ) irradiation and prescription doses of 41.0 Gy [relative biological effectiveness (RBE)]/10 fractions to low-risk (LR) clinical target volume (CTV) plus 24.6 Gy(RBE)/6 fractions to the high-risk (HR) CTV were re-planned with two SIB dose levels to the LR-CTV, namely, 48.0 Gy(RBE) and 54.4 Gy(RBE). While planning with SIB, the HR-CTV coverage had higher priority, with fixed organ-at-risk dose constraints among the SIB and SEQ plans. The homogeneity and conformity indexes were selected for CTV coverage comparison. The biologically effective dose (BED) was calculated to compare the different fractionation schemes.ResultsComparable HR-CTV coverage was achieved with the treatment approaches, while superior conformality and homogeneity were obtained with the SIB technique in both CTVs. With the SEQ, SIB48.0, and SIB54.4, the LR-CTV median doses were respectively 50.3%, 11.9%, and 6.0% higher than the prescriptions. Significant reductions of the median and near-maximum BEDs were achieved with both SIB dose levels in the LR-CTV.ConclusionsThe SIB approach resulted in highly conformal dose distributions with the reduction of the unintended dose to the LR-CTV. A prescription dose range for the LR-CTV will be clinically defined to offer tailored personalized treatments, according to the clinical and imaging characteristics of the patients.

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Adenoid cystic Carcinoma and Carbon ion Only irradiation (ACCO): Study protocol for a prospective, open, randomized, two-armed, phase II study

BMC Cancer ◽

10.1186/s12885-021-08473-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kristin Lang ◽

Sebastian Adeberg ◽

Semi Harrabi ◽

Thomas Held ◽

Meinhard Kieser ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Phase Ii ◽

Local Control ◽

Carbon Ion Radiotherapy ◽

Carbon Ions ◽

Node Negative ◽

Carbon Ion ◽

Adenoid Cystic ◽

High Let

Abstract Background Adenoid cystic carcinoma is a rare form of head and neck cancer with a slow, but aggressive growth pattern which remains a challenge for local tumor control. Based on phase II data, radiation treatment using partially high LET radiation results in a prolonged PFS and OS. There is a paucity of randomized clinical data examining the role of the use of high LET radiation only. Therefore, the purpose of this prospective clinical trial is to analyze local control rates in patients with node negative ACC treated with carbon ion radiotherapy alone compared to a combined modality approach. Methods This trial is conducted as a prospective, open-label, phase II, two-armed, investigator-initiated study comparing the local control rates in node negative ACCs of the head and neck treated either with sole carbon ion radiotherapy or a combination of carbon ions and photons. Secondary outcomes investigated are progression-free survival, overall survival, acute and late toxicity, and quality of life. A total of 314 patients will be randomly assigned to C12 treatment alone or bimodal treatment: Patients in the experimental group will receive a dose of 51 Gy (RBE) in 17 fractions and a boost of 15 Gy (RBE) in 5 fractions. Patients in the control group will receive 25 fractions photon IMRT 50Gy and a boost using 8 × 3 Gy (RBE) carbon ions. Local control will be assessed in regular follow up examinations until 5 years after the completion of treatment. Discussion The present trial aims to evaluate local control rates to compare sole carbon ion radiotherapy to bimodal radiotherapy with carbon ions and photons in patients with node negative ACCs of the head and neck region. Local control is selected as the primary endpoint due to its major clinical relevance because of slow but aggressive growth patterns. Trial registration The study was prospectively registered on 2nd January 2020: ClinicalTrials.gov, NCT04214366. “Adenoid Cystic Carcinoma and Carbon Ion Only Irradiation (ACCO)”. Study status Under recruitment, participant recruitment is not completed. Start of recruitment was January 2020. There are no results been published or submitted to any journal.

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