incidence of secondary cancers after cirt vs rt
Overview of the Study
The risk of secondary cancer after carbon-ion radiotherapy (CIRT) has not been well studied. In this study, the researchers assessed the incidence of secondary cancers in patients who have undergone CIRT for cervical cancer. Aside from CIRT, the researchers also evaluated the incidence of secondary cancers in patients treated with standard photon radiotherapy (RT) during the same timeline.
The researchers believe that this study is the first to investigate the frequency of secondary cancer in patients treated with CIRT for cervical cancer. The study is also the first to investigate the frequency of secondary cancers in patients treated with CIRT for cervical cancer. It is also the first report to directly compare the risk of secondary cancers after CIRT and photon RT for cervical cancer. RT reportedly increases the incidence of secondary cancers by 1.08– 1.43 in the general population.
Cervical cancer is cancer caused by chronic infection with high-risk human papillomavirus. It’s also the most common cancer in women. Annually, the number of cervical cancer cases is estimated to be approximately 569,000.
The standard care for stage I cervical cancer is radiation therapy and concurrent chemo-radiation therapy. With recent technological advancements, RT, including three-dimensional image-guided brachytherapy (3D- IGBT), has become a necessary component of cervical cancer treatment
Carbon-ion radiotherapy (CIRT)
Carbon-ion radiotherapy is deemed to have more advantages over conventional RT. First is the dose localization and biological efficacy due to high linear energy transfer. Currently, CIRT is being used to treat different kinds of cancer including cervical cancer.
The study includes cervical cancer patients that were treated with curative RT. Cancers that were discovered after RT were classified as secondary cancers. The researchers calculated standardized incidence ratios (SIRS) to compare the risk of secondary cancers among cervical cancer survivors.
The subjects included in this retrospective study were patients with uterine cervical cancer who were treated at the National Institutes for Quantum Science and Technology (QST) hospital who received CIRT or photon RT between January 1, 1995, and March 31, 2016.
Patients with distant metastases or synchronous malignancies were excluded from the study. Those who received RT for para-aortic lymph node region or as postoperative irradiation were also excluded.
The detailed regimens of CIRT and photon RT at our hospital have been described elsewhere. Both CIRT and photon RT were administered with curative intent, including whole pelvic irradiation and local tumor irradiation.
However, CIRT was performed as a clinical trial and was not combined with intracavitary brachytherapy. Patients were younger than 70 years, and those who could tolerate this regimen received 40 mg/m2 of cisplatin weekly as concurrent chemotherapy.
The median CIRT dose was 72.0 Gy (relative biological effectiveness [RBE] range, 52.8– 74.4) delivered over a median of 20 fractions over 5 weeks (range, 20– 24 fractions over 5– 6 weeks). Whole pelvic irradiation and central shielding were used in pho-ton RT, with a dose of 2.0 Gy or 1.8 Gy per fraction and a median dose of 50.0 Gy (range, 45.0– 50.6).
Patients with gross lymph node metastases received a 6.0– 10.0 Gy boost RT at the site of the metastasis. Brachytherapy was performed using Ir- 192 with a point A prescription of 6.0 Gy in each fraction, for a total of four fractions (microSelec-Tron HDR; Elekta Instrument AB, Stockholm, Sweden). In-room CT was introduced in 2001, and we shifted from two- dimensional planning to 3D- IGBT.
The researchers collected data from the QST database and medical records on the following: patient age, medical history, smoking and alcohol habits, characteristics and treatment of cervical cancer, and posttreatment course. The Charlson Comorbidity Index was applied to classify patient comorbidities.
For the first 2 years, follow-up was done every 1– 3 months, then every 3– 6 months for the next 3 years; after 5 years, follow-up was done every 6– 12 months, in principle. Patients who did not receive face-to-face follow-up were mailed a yearly questionnaire with specific questions about cervical cancer recurrence, adverse events after treatment, and the development of secondary cancers.
Additional information on secondary cancers was gathered by calling other doctors, hospitals, and patients or their families. With the Ministry of Justice’s approval, missing patient data were supplemented from the Japanese nationwide registry that includes the date and cause of death.
Based on the analysis, there were a total of 197 and 417 patients in the CIRT and photon RT groups. The total person-years during the observation period were 1052.4 in the CIRT group and 2481.5 in the photon RT group. The SIR for all secondary cancers was 1.1 (95% confidence interval [CI], 0.6– 2.1) in the CIRT group and 1.4 (95% CI, 1.0– 2.1) in the photon RT group. The 10- year cumulative incidence of all secondary cancers was 9.5% (95% CI, 4.0– 21.5) in the CIRT group and 9.4% (95% CI, 6.2– 14.1) in the photon RT group. The CIRT and photon RT groups were not significantly different in incidence (p = 0.268).
Based on the findings of the present study, the risk of developing secondary cancers after CIRT for cervical cancer was approximately 1.1 (95% CI, 0.6– 2.1) times that of the general population, and the risk of developing secondary cancer after photon RT was approximately 1.4 (95% CI, 1.0– 2.1) times that of the general population, consistent with previous reports.
The lower limit of the 95% CI for the SIR of secondary cancers in the CIRT group was below 1.0, indicating no apparent difference from the general population. This result may be due to an insufficient number of secondary cancer cases and observation period.
In recent years, the usefulness of CIRT for hard-to-treat gynecologic tumors, such as malignant melanoma and adenocarcinoma of the uterine cervix, has been demonstrated in systematic reviews.
Based on the findings, the incidence of secondary cancers after CIRT for cervical cancer was similar to that after photon RT. Although the benefits of CIRT seem to outweigh the risk of developing secondary cancer, further follow-up is warranted to establish the clinical benefits of CIRT for gynecologic tumors. The incidence of secondary cancers validation of the research findings after long-term observation is warranted.
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