The Feasibility of Omission of Postoperative Radiotherapy in Japanese Patients With Early Breast Cancer Treated With Breast-Conserving Surgery.

Background This study was aimed at analyzing the impact of postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) on Japanese patients with early-stage breast cancer and exploring the potential of PORT omission. Materials and methods Data from 794 patients with early-stage breast cancer (T1-2, N0-1), who underwent BCS with (n = 310) or without PORT (n = 484) were retrospectively analyzed. Local control (LC) rate and breast cancer-specific survival (BCSS) were compared between the groups that received and did not receive PORT in the whole cohort and low-risk cohort (i.e., the cohort with negative surgical margin, lymph node negativity, and estrogen receptor positivity, excluding young age of 49 or less), and in low-risk subgroup using propensity-score matching. Results PORT was associated with better LC but not BCSS in the total population. In the low-risk cohort, the incidence of local recurrence in patients without and with PORT was 5.3% and 4.8%, respectively, at 10 years (p = 0.591), and 7.8% and 4.8%, respectively, according to propensity-score matching (p = 0.485). Conclusion PORT improved LC in the total population, but not BCSS or overall survival (OS). In the low-risk group analysis (negative surgical margin, lymph node negativity, estrogen receptor positivity, and age 50 years or more), equivalent LC, BCSS, and OS were found including propensity-matched comparison. Therefore, this study showed that the omission of PORT could be a treatment option for low-risk Japanese patients. Further multi-center prospective studies are warranted to validate these findings and reduce the unnecessary burden of PORT for patients and institutions.

The influence of Gleason score ≤ 6 histology on the outcome of high-risk localized prostate cancer after modern radiotherapy.

We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2-177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Re-irradiation for isolated neck recurrence in head and neck tumor: impact of rN category.

Unresectable, isolated lymph node recurrence after radiotherapy is rare but a candidate for re-irradiation. However, severe toxicity is anticipated. Therefore, this study aimed to explore the efficacy and toxicity of re-irradiation in isolated lymph node recurrence of head and neck lesions. We analyzed 46 patients who received re-irradiation for lymph node recurrence without local progression. The primary tumor sites included the oral cavity in 17 patients, the hypopharynx in 12, the oropharynx in seven, the larynx in three, the nasopharynx in two, and other sites. During a median follow-up time of 10 months, the median survival time was 10.6 months, and the 1-year overall survival rate was 45.5%. The 1-year local control and progression-free survival rates were 49.8% and 39.3%, respectively. According to univariate analysis, age (≥ 65 years), the interval between treatment (≥ 12 months), rN category (rN1), and gross tumor volume (GTV < 25 cm3) were predisposing factors for better survival. In the multivariate analysis, the rN category and interval were identified as statistically significant predictors. Late toxicity grade ≥ 3 occurred in four patients (8.6%). These were all Grade 5 carotid blowout syndrome, which associated with tumor invasion of the carotid artery and/ or high doses administration for the carotid artery. Small-volume rN1 tumor that recur after a longer interval is a feasible candidate for re-irradiation. However, strict patient selection and meticulous care for the carotid are required.

Comparative dosimetric study of spot-scanning proton therapy versus volumetric-modulated radiation therapy for extrahepatic bile duct cancer.

This study aimed to compare the dose distributions and clarify the dosimetric characteristics of spot-scanning proton therapy (SSPT) and photon volumetric modulated arc therapy (VMAT) for extrahepatic bile duct cancer (EBDC). This retrospective study included 10 patients with EBDC treated with real-time image-gated SSPT. Using the simultaneous integrated boost technique, the 2 prescription dose levels for planning target volumes were 72.6 and 44 Gy, delivered in 22 fractions. Plan quality comparisons were conducted by analyzing various parameters, including homogeneity, conformity, dose to organs at risk, and normal tissue complication probability (NTCP) for radiation-induced liver damage (RILD). The target dose distributions using SSPT were almost equivalent to those achieved using photon VMAT. There was a significant reduction in all liver dose parameters, the NTCP value for RILD, and kidney dose (mean, V12 Gy, and V18 Gy) in SSPT than in photon VMAT. No significant differences were observed in the intestinal doses in the high-dose area. Thus, compared with photon VMAT, SSPT for EBDC significantly reduced radiation doses to the liver and kidneys and has shown potential clinical benefits of reduced radiation-induced toxicity.

Increasing rectum-prostate distance using a hydrogel spacer to reduce radiation exposure during proton beam therapy for prostate cancer.

SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level < 7.5 mm, n = 81), and 2 (distance ≥ 7.5 mm, n = 108). The rectal volumes to receive 30-60 Gy (RBE), was estimated and described as Rectal V30-60 (ml) in 10 Gy increments. The Rectal V30-60 (ml) was significantly lower in group 2 than in group 1, and in group 1 than in group 0. After propensity score matching, the multivariate logistic regression analysis revealed that the most significant factor to reduce radiation exposure was our modified technique of hydrogel insertion. Therefore, using a hydrogel spacer to expand the prostate-rectum distance not only at prostate-mid to prostate-base level but also at the prostate-apex level can reduce the radiation exposure in PBT for prostate cancer.

Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.

Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5 cm.

Reirradiation for local recurrence of oral, pharyngeal, and laryngeal cancers: a multi-institutional study.

This study aimed to examine the efficacy and toxicity of reirradiation in patients with locally recurrent oral, pharyngeal, and laryngeal cancers. We conducted a retrospective, multi-institutional analysis of 129 patients with previously irradiated cancer. The most frequent primary sites were the nasopharynx (43.4%), oral cavity (24.8%), and oropharynx (18.6%). With a median follow-up duration of 10.6 months, the median overall survival was 14.4 months and the 2-year overall survival rate was 40.6%. For each primary site, the 2-year overall survival rates were 32.1%, 34.6%, 30%, 60.8%, and 5.7% for the hypopharynx, oral cavity, larynx, nasopharynx, and oropharynx, respectively. Prognostic factors for overall survival were primary site (nasopharynx versus other sites) and gross tumor volume (GTV) (≤ 25 cm3 versus > 25 cm3). The 2-year local control rate was 41.2%. Twenty-four patients (18.6%) presented with grade ≥ 3 toxicities, including nine with hemorrhages that led to grade 5 toxicities in seven patients. All nine tumors that caused hemorrhage showed tumor encasement of the carotid ≥ 180 degrees and eight of nine tumors had larger GTV > 25 cm3. Reirradiation is a feasible treatment option for small local recurrence of oral, pharyngeal, and laryngeal cancers, with the requirement of a strict eligibility assessment for large tumors with carotid encasement.

Palliative Radiation Therapy for Intramedullary Spinal Cord Metastasis.

BACKGROUND/AIM: The purpose of this study was to retrospectively review the outcomes of intramedullary spinal cord metastasis (ISCM) and identify predictors for ambulation after radiotherapy (RT). PATIENTS AND METHODS: We analyzed 16 lesions in 15 patients treated with RT for ISCM at our clinic from October 2009 to April 2020 to evaluate predictors for improved ambulation following RT. RESULTS: The primary diseases included nine cases of lung cancer, two cases of breast cancer, and several others. The RT schedule was primarily 30 Gy/10 fractions in seven cases, while others were applied to nine cases. The median overall survival time was 99 days. After RT, all seven patients who could walk prior to RT were still able to walk (100%), whereas only two of nine patients who could not walk prior to RT were able to walk (22%, p=0.004). CONCLUSION: Ambulation prior to RT was a significant predictor of ambulation ability after RT.

Chemoradiation versus surgery for superficial esophageal squamous cell carcinoma after noncurative endoscopic submucosal dissection: comparison of long-term oncologic outcomes.

BACKGROUND: Esophagectomy is the standard adjuvant treatment for superficial esophageal squamous cell carcinoma (SESCC) following noncurative endoscopic submucosal dissection (ESD). However, recent reports have also shown that ESD with adjuvant chemoradiotherapy (CRT) has promising results. This retrospective study aimed to elucidate the efficacy of CRT compared to surgery in patients with SESCC after noncurative ESD. METHODS: This study retrospectively compared the long-term outcomes of patients who received adjuvant treatment with surgery or CRT after noncurative ESD for SESCC. RESULTS: Data were collected from 60 patients who developed SESCC after noncurative ESD, 34 of whom received adjuvant chemoradiotherapy (CRT) and 26 underwent esophagectomy. The median follow-up periods were 46 and 56 months in the CRT and esophagectomy groups, respectively. The median patient age was significantly higher in the CRT group than in the esophagectomy group (69 vs. 65 years, p = 0.0054). CRT was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The overall and disease-free survival did not significantly differ between the two groups. CONCLUSIONS: CRT following ESD seems a promising nonsurgical strategy for optimizing the selection of therapies for high-risk SESCC and warrant further investigation.

＜Editors' Choice＞ Elective nodal irradiation versus involved field radiotherapy for limited disease small cell lung cancer: a single-institution experience.

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with limited-disease small cell lung cancer (LD-SCLC). However, no solid consensus exists on their optimal target volume. The current study aimed to assess the clinical outcomes of patients with LD-SCLC who received definitive ENI or IFRT. A retrospective single-institution study of patients who received definitive radiotherapy between 2008 and 2020 was performed. All patients underwent whole-body positron emission tomography/computed tomography before three-dimensional conformal radiotherapy. Among the 37 patients analyzed, 22 and 15 received ENI and IFRT, respectively. The thoracic radiotherapy dose was mostly either 60 Gy in 30 fractions delivered in 2-Gy fractions once daily or 45 Gy in 30 fractions delivered in 1.5-Gy fractions twice daily. The median follow-up period was 21.4 months. A total of 12 patients (32%) experienced locoregional relapse: 10 within and 2 outside the irradiation fields. One patient in the IFRT group experienced isolated nodal failure. Differences in locoregional relapse-free, progression-free, and overall survival rates between ENI and IFRT were not significant. Overall, IFRT did not promote a significant increase in locoregional recurrence compared to ENI. Our findings suggested the utility of IFRT in standard clinical practice and support its use for patients with LD-SCLC.

Role of Brachytherapy Boost in Clinically Localized Intermediate and High-Risk Prostate Cancer: Lack of Benefit in Patients with Very High-Risk Factors T3b-4 and/or Gleason 9-10.

This study examined the role of brachytherapy boost (BT-boost) and external beam radiotherapy (EBRT) in intermediate- to high-risk prostate cancer, especially in patients with very high-risk factors (VHR: T3b-4 or Gleason score 9-10) as patients with double very high-risk factors (VHR-2: T3b-4 and Gleason score 9-10) previously showed worst prognosis in localized prostate cancer. We retrospectively reviewed multi-institutional data of 1961 patients that were administered radiotherapy (1091 BT-boost and 872 EBRT: 593 conventional-dose RT (Conv RT: equivalent to doses of 2 Gy per fraction = EQD2 ≤ 72 Gy) and 216 dose-escalating RT (DeRT = EQD2 ≥ 74 Gy). We found that BT-boost improved PSA control and provided an equivalent overall survival rate in the intermediate- and high-risk groups, except for patients within the VHR factor group. In the VHR-1 group (single VHR), BT-boost showed a superior biochemical control rate to the Conv RT group but not to the DeRT group. In the VHR-2 group, BT-boost did not improve outcomes of either Conv RT or DeRT groups. In conclusion, BT-boost showed no benefit to modern DeRT in the patients with VHR; therefore, they are not good candidates for BT-boost to improve outcome and may be amenable to clinical trials using multimodal intensified systemic treatments.

Optimal Clinical Target Volume of Radiotherapy Based on Microscopic Extension around the Primary Gross Tumor in Non-Small-Cell Lung Cancer: A Systematic Review.

A crucial issue in radical radiation therapy for non-small-cell lung cancer is how to define the clinical target volume (CTV). Although the scope of microscopic extension (ME) and microscopic proximal bronchial extension (PBE) from a primary tumor should be considered when defining the CTV, there has been limited research on ME and PBE. Therefore, we conducted this systematic review. The PubMed, ICHUSHI (Japanese database), and Cochrane Library databases were searched, and 816 articles were initially retrieved. After primary and secondary screenings, eight articles were ultimately selected. The results of this systematic review suggest the importance of a 0 mm margin in stereotactic radiotherapy for early-stage cancer and a 5-8 mm margin in curative irradiation for locally advanced cancer. Regarding PBE, this review yielded the conclusion that it is appropriate to consider the addition of an approximately 15 mm margin from the bronchial vasculature. Although there were few articles with a high level of evidence, this systematic review enabled us to collate results from previous studies and to provide recommendations, to some extent, regarding the CTV margin in the current clinical environment, where high-precision radiation therapy, such as image-guided radiotherapy and intensity-modulated radiotherapy, is predominant.

Reirradiation for Rare Head and Neck Cancers: Orbit, Auditory Organ, and Salivary Glands.

We analyzed the efficacy and toxicity following reirradiation for locoregional recurrence of rare head and neck tumors. We retrospectively analyzed 17 patients who had received reirradiation for rare head and neck tumors. Primary tumor sites included nine ears (auditory organ), four salivary glands, and four orbits. The median follow-up time was 13.2 months for surviving patients. The median survival time was 12.6 months with one- and two-year survival rates of 53.1% and 44.3%, respectively. Nine out of 17 patients experienced local failure. The one- and two-year local control rates were 42.4% and 31.8%, respectively. The median survival times were 12.6, 5.3, and 11.0 months for orbit, auditory organ, and salivary glands, respectively. Three patients experienced grade 3 toxicity, including meningitis, brain necrosis, and facial nerve disorders. No grade ≥4 toxicities were observed. Reirradiation of rare head and neck tumors is feasible, with acceptable toxicity.

Comparison of toxicities between ultrahypofractionated radiotherapy versus brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer.

To compare gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with ultrahypofractionated radiotherapy (UHF) or brachytherapy [BT; low dose rate, LDR or high dose rate (HDR) with or without external beam radiotherapy (EBRT)]. We compared 253 UHF and 1664 BT ± EBRT groups. The main outcomes were the incidence and severity of acute and late GU and GI toxicities. The secondary endpoint was biochemical control rate. Cumulative late actuarial GU toxicity did not differ for grade ≥ 2 (8.6% at 5-years in UHF and 13.3% in BT ± EBRT, hazard ratio [HR], 0.7066; 95% CI, 0.4093-1.22, p = 0.2127). Actuarial grade ≥ 2 late GI toxicity was higher in UHF (5.8% at 5-years, HR: 3.619; 95% CI, 1.774-7.383, p < 0.001) than in BT ± EBRT (1.1%). In detailed subgroup analyses, the high-dose UHF group (H-UHF) using BED ≥ 226 Gy1.5, showed higher GI toxicity profiles than the other subgroups (HDR + EBRT, LDR + EBRT, and LDR monotherapy, and L-UHF BED < 226 Gy1.5) with equivalent GU toxicity to other modalities. With a median follow-up period of 32 months and 75 months, the actuarial biochemical control rates were equivalent between the UHF and BT ± EBRT groups. UHF showed equivalent efficacy, higher GI and equivalent GU accumulated toxicity to BT ± EBRT, and the toxicity of UHF was largely dependent on the UHF schedule.

Conventional dose versus dose escalated radiotherapy including high-dose-rate brachytherapy boost for patients with Gleason score 9-10 clinical localized prostate cancer.

As several recent researches focus on the importance of Gleason 9-10, we examine the role of radiotherapy dose escalation in those patients. We analyzed 476 patients with Gleason score 9-10 prostate cancer treated with radiotherapy. Of them, 127 patients were treated with conventional-dose external beam radiotherapy (Conv RT) and 349 patients were treated with high-dose radiotherapy (HDRT; 249 patients received high-dose-rate brachytherapy boost + external beam radiotherapy [HDR boost] and 100 patients received intensity-modulated radiotherapy [IMRT]). We compared these treatment groups using multi-institutional retrospective data. The patients had a median follow-up period of 66.3 months. HDRT showed superior biochemical disease-free survival (bDFS) rate (85.2%; HDR boost 84.7% and IMRT 86.6%) to Conv RT (71.1%, p < 0.0001) at 5 years, with a hazard ratio of 0.448. There were borderline difference in prostate cancer-specific mortality (PCSM; 4.3% and 2.75%, p = 0.0581), and distant metastasis-free survival (DMFS; 94.4% and 89.6%, p = 0.0916) rates at 5-years between Conv RT and HDRT group. Dose escalated radiotherapy showed better bDFS, borderline improvement in PCSM, and equivocal outcome in DMFS in with clinically localized Gleason 9-10 prostate cancer.

Reirradiation for Nasal Cavity or Paranasal Sinus Tumor-A Multi-Institutional Study.

We evaluated the efficacy and toxicity of reirradiation of nasal cavity or paranasal sinus tumors. We collected and analyzed multi-institutional data of reirradiation cases. Seventy-eight patients with nasal or paranasal sinus tumors underwent reirradiation. The median survival time was 20 months with a medial follow-up of 10.7 months. The 2-year local control and overall survival rates were 43% and 44%, respectively. Tumor volume (≤25 cm3), duration between previous radiotherapy and reirradiation (≤12 months), histology (squamous cell carcinoma), male sex, and lymph node involvement were predisposing factors for poor survival. Distant metastasis was observed in 20 patients (25.6%). Grade ≥ 3 adverse events were observed in 22% of the patients, including five grade 4 (8.6%) cases and one grade 5 (1.2%) case. Tumor location adjacent to the optic pathway was a significant predisposing factor for grade ≥3 visual toxicity. Reirradiation of nasal and paranasal sinus tumors is feasible and effective. However, adverse events, including disease-related toxicities, were significant. Prognostic factors emerge from this study to guide multidisciplinary approaches and clinical trial designs.

Novel Prognostic Index of High-Risk Prostate Cancer Using Simple Summation of Very High-Risk Factors.

This study aimed to examine the role of very high-risk (VHR) factors (T3b-4 and Gleason score 9-10) for prognosis of clinically localized high-risk prostate cancer. We reviewed multi-institutional retrospective data of 1413 patients treated with radiotherapy (558 patients treated with external beam radiotherapy (EBRT) and 855 patients treated with brachytherapy (BT) ± EBRT. We introduced an index by simple summation of the number of VHR factors-VHR-0, VHR-1, and VHR-2. With median follow-up of 69.6 months, the 5-year biochemical disease free survival rate (bDFS), prostate cancer-specific mortality (PCSM), and distant metastasis-free survival (DMSF) rates were 59.4%, 7.65%, and 83.2% for the VHR-2 group, respectively; 86.7%, 1.50%, and 95.4% for the VHR-1 group, respectively; and 93.1%, 0.12%, and 98.2% for the VHR-0 group, respectively. The VHR-2 group had significantly worse bDFS, PCSM, and DMSF than the VHR-0 (hazard ratios: 4.55, 9.607, and 7.904, respectively) and VHR-1 (hazard ratios: 1.723, 2.391, and 1.491, respectively) groups. The VHR-2 group could be identified as a super high-risk group compared with other groups, and could be a good candidate for clinical trials using multimodal intensified treatments. Simple summation of the number of VHR factors is an easy and useful predictive index for bDFS, PCSM, and DMSF.