Functional Image-Guided Radiotherapy Planning in Respiratory- Gated Intensity-Modulated Radiation Therapy (IMRT) for Lung Cancer Patients with chronic obstructive pulmonary disease (COPD)

(Purpose) To investigate the incorporation of functional lung image-derived low attenuation area (LAA) based on four-dimensional computed tomography (4D-CT) into respiratory-gated intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) in treatment planning for lung cancer patients with chronic obstructive pulmonary disease (COPD). (Materials and Methods) Eight lung cancer patients with COPD were the subjects of this study. LAA was generated from 4D-CT data sets according to CT values lower than -860 Hounsfield units (HU) as a threshold. The functional lung image was defined as the area where LAA was excluded from the image of the total lung. Two respiratory-gated radiotherapy plans (70 Gy/35 fr) were designed and compared in each patient as follows: 1) Plan A: anatomical IMRTor VMAT plan based on the total lung 2) Plan F: functional IMRT or VMAT plan based on the functional lung. Dosimetric parameters (V20: the percentage of total lung volume irradiated with ≥ 20 Gy,MLD:mean dose of total lung) of the two plans were compared. (Results) V20 was lower in Plan F than in Plan A (mean 1.5 %, p= 0.025 in IMRT, mean 1.6 %, p= 0.044 in VMAT) achieved by a reduction in MLD (mean 0.23 Gy, p= 0.083 in IMRT, mean 0.5 Gy, p= 0.042 in VMAT). No differences were noted in target volume coverage and organ-at-risk doses. (Conclusions) Functional image-guided radiotherapy planning based on LAAin respiratory-guided IMRT or VMAT appears to be effective in preserving a functional lung in lung cancer patients with COPD.This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant no. 22591385), and a Grant-in-Aid for Scientific Research from the Association for Nuclear Technology in Medicine. This work was partly presented at the 52nd Annual Meeting of the American Society of Radiation Oncology, San Diego, CA, Oct 31 - Nov 4, 2010

CT-based CTVHR for cervical brachytherapy

Our purpose was to develop recommendations for contouring the computed tomography (CT)-based high-risk clinical target volume (CTVHR) for 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. A 15-member Japanese Radiation Oncology Study Group (JROSG) committee with expertise in gynecological radiation oncology initiated guideline development for CT-based CTVHR (based on a comprehensive literature review as well as clinical experience) in July 2014. Extensive discussions occurred during four face-to-face meetings and frequent email communication until a consensus was reached. The CT-based CTVHR boundaries were defined by each anatomical plane (cranial–caudal, lateral, or anterior–posterior) with or without tumor progression beyond the uterine cervix at diagnosis. Since the availability of magnetic resonance imaging (MRI) with applicator insertion for 3D planning is currently limited, T2-weighted MRI obtained at diagnosis and just before brachytherapy without applicator insertion was used as a reference for accurately estimating the tumor size and topography. Furthermore, utilizing information from clinical examinations performed both at diagnosis and brachytherapy is strongly recommended. In conclusion, these recommendations will serve as a brachytherapy protocol to be used at institutions with limited availability of MRI for 3D treatment planning

SCC antigen and ApoC-II as serum biomarkers of cervical cancer

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer

Prediction of recurrence after chemoradiotherapy

We retrospectively assessed whether magnetic resonance imaging (MRI) radiomics combined with clinical parameters can improve the predictability of out-of-field recurrence (OFR) of cervical cancer after chemoradiotherapy. The data set was collected from 204 patients with stage IIB (FIGO: International Federation of Gynecology and Obstetrics 2008) cervical cancer who underwent chemoradiotherapy at 14 Japanese institutes. Of these, 180 patients were finally included for analysis. OFR-free survival was calculated using the Kaplan–Meier method, and the statistical significance of clinicopathological parameters for the OFR-free survival was evaluated using the log-rank test and Cox proportional-hazards model. Prediction of OFR from the analysis of diffusion-weighted images (DWI) and T2-weighted images of pretreatment MRI was done using the least absolute shrinkage and selection operator (LASSO) model for engineering image feature extraction. The accuracy of prediction was evaluated by 5-fold cross-validation of the receiver operating characteristic (ROC) analysis. Para-aortic lymph node metastasis (p = 0.003) was a significant prognostic factor in univariate and multivariate analyses. ROC analysis showed an area under the curve (AUC) of 0.709 in predicting OFR using the pretreatment status of para-aortic lymph node metastasis, 0.667 using the LASSO model for DWIs and 0.602 using T2 weighted images. The AUC improved to 0.734 upon combining the pretreatment status of para-aortic lymph node metastasis with that from the LASSO model for DWIs. Combining MRI radiomics with clinical parameters improved the accuracy of predicting OFR after chemoradiotherapy for locally advanced cervical cancer

QOL after RT or OP for uterine cervix cancer

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important

Early clinical outcomes of 3D-conformal radiotherapy using accelerated hyperfractionation without intracavitary brachytherapy for cervical cancer

Purpose/Objective: To evaluate the outcome of cervical cancer patients unable to undergo conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT) alone using accelerated hyperfractionation (AHF). Methods and Materials: We reviewed the records of 7 patients who had received definitive radiotherapy with 3DCRT alone using AHF for cervical cancer between 2002 and 2005. FIGO stage was IB (1), IIB (2), IIIA (1), IIIB (2), and IVA (1). The reason we did not perform ICBT was due to patient refusal. In 1 patient with stage IB, a total dose of 65.4 Gy was delivered by local irradiation (LI) only. In 1 patient with stage IIIA, a total dose of 60 Gy was delivered by LI only. In 5 patients with Stage IIB-IV, a median total dose of 70.8 Gy was delivered by combination of whole pelvic irradiation (median dose of 45 Gy) with LI. Median overall treatment time was 42 days. Results: Median follow-up for survival patients was 17 months. Out of 7 patients, 6 patients had CR and 1 patient had PR. The response rate was 100%.0 The 2-year local control rate was 85.7%.0 Of these patients, 5 are alive without disease and 1 is alive with lung metastasis. Conclusions: Our outcomes suggest that 3DCRT using AHF may be a promising as a definitive treatment for cervical cancer when ICBT is not able to be performed

Evaluation of the basic properties of the BANGkit™ gel dosimeter

We evaluated the basic properties of a commercially available BANGkit™ gel dosimeter, which is a normoxic type of BANG® gel. This gel-kit has the same composition as the BANG®3 gel, but is fully oxygenated. To exclude oxygen, oxygen scavenging ascorbic acid and copper sulfate as a catalyst are used. The properties that we examined are the effects of the concentrations of copper sulfate and ascorbic acid on the response, the reproducibility, the long-term stability, the temperature effect at irradiation, and the dose-rate effect. In our results, the excellent linear fit of the R2-dose response in a dose range for clinical use and its reproducibility were observed. The precision of a linear fit was preserved for about three weeks. The temperature at irradiation showed a significant effect on the dose response. Although the dose-rate dependence in the high dose range was observed, it was negligible for the clinical dose range up to 270 cGy. In conclusion, this gel dosimeter is thought to be utilizable in clinical practice, while we have to pay attention to the temperature during the entire measurement processes, and additionally there is room for improvement in the linearity and the dose-rate dependence in the high dose range

A Survey of Patients with Inflammatory Skin Recurrence Corresponding to the Area of Previous Irradiation after Postoperative Radiotherapy for Breast Cancer

One of the unusual patterns of local recurrence in breast cancer patient is an inflammatory skin recurrence (ISR) sharply demarcating the area of previous radiation fields. To clarify the characteristics of this recurrence, we conducted a nationwide survey. We sent a survey to radiation oncologists at 200 institutions in Japan and received answers from 92. Of these, 24 institutions had some experience with patients who developed ISR affecting the previously irradiated area. The case details of 16 patients from 11 institutions were available and analyzed in this study. Eight patients experienced ISR after breast conservative therapy (groupA) and 8 patients experienced ISR after post-mastectomy radiotherapy (groupB). The postoperative pathological examination of groups A and B showed positive axillary lymph-nodes in 7/8 and 8/8 patients, positive lymphatic invasion in 4/7 and 7/8 patients, and ER status negative in 7/8 and 6/7 patients respectively. Median survival period was 266 days in groupA and 1105 days in groupB (p = 0.0001). Patients who developed the ISR tended to have several characteristics, including positive lymph-node metastases, intensive lymphatic invasion, and ER status negative. Physicians should contemplate the diagnosis of ISR next to radiation recall or radiation dermatitis, especially when the aforementioned risk factors are present