Radiotherapy for ductal carcinoma of the prostate: an analysis based on the Japanese radiation oncology study group survey.

BACKGROUND: The clinical characteristics of prostate ductal carcinoma is still unclear, and treatment strategy has not yet been established due to its rarity. Therefore, we conducted a multicenter survey of radiation therapy for prostate ductal carcinoma in Japan. METHOD: Data of patients with ductal carcinoma of the prostate treated with radiation therapy between 1996 and 2018 were extracted from the database of each facility. RESULTS: Fifty-two treatment records of 41 patients were collected from nine institutions. The treatment purpose and situations were varied curative intent to palliation. Twenty-eight patients received curative treatments. The median follow-up period of these patients was 68 months. Androgen deprivation therapy was combined with radiation therapy in 26 cases (93%). X-ray and particle irradiation was used. Radiation dose range was 63-78 Gy; 5-year overall survival, progression-free survival and biochemical relapse-free survival were 87.0, 79.3 and 79.3%, respectively. One patient experienced Grade 3 radiation proctitis and one experienced Grade 3 radiation cystitis. There were no Grade 4 or worse adverse events. CONCLUSION: Most patient received similar treatment with adenocarcinoma of prostate, and the clinical results were compatible. For more reliable evidence, further studies are required.

Daily irradiation versus irradiation at two- to three-day intervals in stereotactic radiotherapy for patients with 1-5 brain metastases: study protocol for a multicenter open-label randomized phase II trial.

BACKGROUND: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM). METHODS: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728. DISCUSSION: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now. TRIAL REGISTRATION: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000055515 .

Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial.

BACKGROUND: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT). METHODS: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death. RESULTS: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722). CONCLUSIONS: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa.

Patient selection for salvage surgery after definitive chemoradiotherapy in esophageal squamous cell carcinoma.

PURPOSE: With the widespread use of definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC), salvage surgery for recurrence/residual patients became prevalent. However, survival impact of salvage surgery remains obscure at present. METHODS: The updated clinical outcomes of salvage surgery were investigated to know its survival impact. Of the 155 ESCC patients who underwent dCRT between 2009 and 2016, we included 85 patients with recurrence or residual disease. The median follow-up was 65 months. RESULTS: Of the 85 patients with progression disease, there were 42 and 43 patients of recurrence and residual disease, respectively. Salvage surgery was performed in 27 patients after dCRT, including 15 patients who underwent salvage esophagectomy. The 5-year overall survival (OS) of salvage surgery and otherwise patients was 66.1% and 14.5%, and the patients with salvage surgery had a significantly better prognosis (p < 0.0001). In the 15 patients who underwent salvage esophagectomy, residual disease, lymph node metastasis-positive (ycN+) after dCRT, and pathological lymph node metastasis-positive (ypN+) were significantly associated with poor prognosis (p = 0.0492, p = 0.0006, p = 0.0276), and the 5-year OS rates for the ycN/ypN combinations were 90%, 33.3%, and 0% in ycN-/ypN-, ycN+/ypN-, and ycN+/ypN+ patients, respectively (p = 0.0026). In a multivariate analysis, ycN+ was an independent poor prognostic factor (HR 13.6, 95% CI 1.65-286.8, p = 0.0154). CONCLUSIONS: Survival impact of salvage surgery after dCRT is robust, and lymph node metastasis after dCRT may help determine the indication for salvage esophagectomy.

A retrospective study of definitive chemoradiotherapy in patients with resectable small cell neuroendocrine carcinoma of the esophagus.

BACKGROUND: Standard treatment for resectable small cell neuroendocrine carcinoma of the esophagus (SCNEC-E) remains to be established. METHODS: We retrospectively studied 7 consecutive patients with resectable SCNEC-E who received definitive chemoradiotherapy (dCRT) to evaluate the safety and efficacy. Treatment consisted of two courses of chemotherapy with cisplatin (80 mg/m2 on day 1) and etoposide (100 mg/m2 on days 1-3) or carboplatin (AUC 5 on day 1) and etoposide (80 mg/m2 on days 1-3) given every 4 weeks during dCRT. The total radiation dose was 50.4 Gy (28 fractions). RESULTS: The clinical stage was IA in 1 patient, IB in 2 patients, IIA in 3 patients, and IIB in 1 patient. Definitive CRT was completed in all patients. The median overall treatment time of radiotherapy was 44 days. The chemotherapy regimen included in dCRT was cisplatin and etoposide in 3 patients and carboplatin and etoposide in 4 patients. Acute adverse events of grade 3 or 4 were neutropenia 100%, thrombocytopenia 43%, febrile neutropenia 43%, and nausea 14%. There were no late grade 3 or 4 adverse events. The median survival time was 32 months. The complete response rate was 100%. The recurrence rate was 43%. The median survival of the 4 patients without recurrence was 56 months. CONCLUSIONS: Definitive CRT with cisplatin and etoposide or carboplatin and etoposide is a feasible treatment for the resectable SCNEC-E, and long-term survival can be achieved in some patients.

Long-term outcomes of combining prostate brachytherapy and metastasis-directed radiotherapy in newly diagnosed oligometastatic prostate cancer: A retrospective cohort study.

BACKGROUND: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial showed the survival benefit for prostate radiotherapy in newly diagnosed prostate cancer patients with a low metastatic burden. The result raises the next question whether additional radiotherapy to metastatic sites could improve the survival in those with a low metastatic burden. METHODS: We evaluated the efficacy and safety of prostate-directed radiotherapy (PDRT) with or without metastasis-directed radiotherapy (MDRT) in newly diagnosed oligometastatic patients who underwent combination of high-dose-rate prostate brachytherapy, external beam radiotherapy, and androgen deprivation therapy. Forty patients with bone metastasis and node positive prostate cancer were retrospectively analyzed. Of these, 22 (55%), 3 (7%), and 15 (38%) patients had N1M0, M1a, and M1b, respectively. Eighteen patients (45%) received MDRT to all metastatic sites. All patients initially underwent ≧6 months of androgen deprivation therapy. Oligometastatic disease was defined as presence of five or fewer metastatic lesions. Median follow-up period was 62.5 months. RESULTS: Of the 40 patients, the 5-year castration-resistant prostate cancer (CRPC)-free survival rate and cancer-specific survival was 64.4% and 87.9%, respectively. Pre- or post-treatment predictive value including prostate-specific antigen (PSA) at diagnosis ≥20 ng/mL, Gleason grade group 5, positive biopsy core rate ≥51%, PSA nadir level of ≥0.02 ng/mL after the radiotherapy, and no MDRT were significantly associated with progression to CRPC. Patients with MDRT had significantly higher probability of achieving a PSA level of <0.02 ng/mL than those without the therapy (88.8% vs 54.5%, P = 0.0354) and consequently had a better CRPC-free survival than those without the therapy (HR 0.319, 95%CI: 0.116-0.877). Comparing PDRT alone, PDRT with MDRT did not significantly increase the incidences of genitourinary and gastrointestinal toxicities. CONCLUSIONS: This single-institutional study revealed the feasibility of combining prostate brachytherapy and MDRT for newly diagnosed oligometastatic prostate cancer. This combined approach has potential to prolong CRPC-free survival.

Quality of life outcomes after low dose-rate brachytherapy for localized prostate cancer: Current status and future perspectives.

The present review summarizes data from studies reporting on health-related quality of life after brachytherapy and competing modalities. There are various therapeutic modalities for localized prostate cancer, including radical surgery, external beam radiotherapy and active surveillance. Advances in surgical and radiation treatment have entered clinical practice in the form of robot-assisted surgery or intensity-modulated radiotherapy. Brachytherapy remains the main treatment option for patients with localized prostate cancer, with 10-year survival data showing favorable outcomes. Because each treatment modality has achieved favorable survival outcomes, focus in determining appropriate treatment has shifted toward health-related quality of life, where each treatment has a different profile and/or adverse symptoms. The development of health-related quality of life assessment tools has allowed the creation of a pool of specific health-related quality of life data across many studies. The present article reviews the impact of brachytherapy and other modalities on quality of life, as well as future directions.

Impact of five-tiered Gleason grade groups on prognostic prediction in clinical stage T3 prostate cancer undergoing high-dose-rate brachytherapy.

BACKGROUND: We evaluated a five-tiered Gleason grade groups arising from the 2014 International Society of Urological Pathology consensus conference on prognostic prediction in clinical stage T3a (extracapsular invasion) and T3b (seminal vesicle involvement) prostate cancer undergoing high-dose-rate brachytherapy (HDR-BT). METHODS: From November 2003 to December 2012, 283 patients with stage T3 prostate cancer received HDR-BT and external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT). Of these, 203 (72%) and 80 (28%) patients had stage T3a and T3b disease, respectively. The mean dose to 90% of the planning target volume was 7.5 Gy/fraction of HDR-BT. After five fractions, EBRT with 10 fractions of 3 Gy was administered. All patients first underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT continued for 36 months. Median follow-up was 74 months from the start of radiotherapy. RESULTS: The 10-year biochemical recurrence (BCR) -free rate for stage T3a and T3b disease was 79% and 64%, respectively (P = 0.0083). The 10-year cancer-specific survival (CSS) rate for stage T3a and T3b was 96% and 91%, respectively (P = 0.0305). Although grade groups ≥4 were independent predictors for BCR in cT3a patients (P = 0.0270), they failed to significantly predict prostate cancer-specific mortality (PCSM) among cT3a patients. Among cT3b patients, grade group 5 was a significant predictor of both BCR (P = 0.0017) and PCSM (P = 0.0233). Among stage T3a patients, no significant difference existed in 10-year CSS between grade groups 5 and 4 (94% vs 97%, P = 0.3960). In contrast, grade group 5 had a significantly worse outcome in 10-year CSS than grade group 4 among stage T3b patients (74% vs 100%, P = 0.0350). CONCLUSIONS: Stage T3a patients with grade groups 4/5 and stage T3b with grade group 4 had fairly low PCSM risk. Approximately one of four patients among stage T3b patients with grade group 5 showed PCSM after combined HDR-BT and EBRT with long-term ADT. Stage T3b patients with grade group 5 may have a greater risk for PCSM.

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer.

Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT). Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative) and again immediately after the surgical manipulation (intraoperative). Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs) using the CellSearch System. While no preoperative samples showed CTCs (0%), they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012). Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA) at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

Current multidisciplinary approaches for metastatic prostate cancer.

Prostate cancer incidences in most Asian populations have rapidly increased, and prostate cancer ranks as the highest incidence of male cancer in Japan since 2015. Androgen depriva- tion therapy (ADT) remains the main first-line treatment for patients with metastatic prostate cancer (mPCa). However, treatment benefits last for 3-5 years when disease transforms into metastatic castration-resistant prostate cancer (mCRPC). Currently, management paradigms for mPCa are dramatically changing. Two multicenter, randomized trials have redefined first-line treatment, with the demonstration of improved overall survival with the addition of docetaxel chemotherapy to ADT. Several data have re- ported the impact on survival of radiotherapy of the prostate even in patients diagnosed with mPCa. The objective of this review is to summarize an overview of current multidisciplinary approaches for mPCa and mCRPC.

[Current diagnosis and the multidisciplinary approach to the treatment of bone metastases in patients with prostate cancer].

Prostate cancer is now the most commonly diagnosed cancer in Japanese men. In 2015, it is estimated 98,400 new cases are diagnosed. In addition, bone is the most common site for metastasis in prostate cancer, and many patients will develop bone metastases during the natural course of their disease. However, current advances in the diagnosis/treatment of metastatic prostate cancer, lead to change treatment strategy dramatically. In fact, bone metastasis has been changed 'palliative' to 'targeted organ', aimed to extend overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We review the multiple issues involved in current diagnosis and the multidisciplinary approach to the treatment of bone metastases in patients with prostate cancer, and future directions.

Clinical outcomes of 849 laryngeal cancers treated in the past 40 years: are we succeeding?

OBJECTIVE: We analyzed the clinical outcomes of 849 laryngeal cancers treated in the past 40 years, which overlapped with the era of the global treatment shift. METHODS: To compare the chronological outcomes, patients were divided into four groups according to their registration year as 1972-82, 1983-92, 1993-2002 and 2003-12; treatment trends, larynx preservation rate and overall survival rate were compared. RESULTS: There were 104, 173, 253 and 319 patients registered in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. Five-year overall survival rates were 74, 76.5, 75.6 and 82.2% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. The five-year larynx preservation rates were 65.5, 75.7, 75.4 and 80.9% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. CONCLUSIONS: The number of patients treated at our institute increased, and the overall survival and larynx preservation rates exhibited favorable improvements over the past four decades. In the analysis of nonsurgical options, S1 combined radiotherapy showed superiority over concurrent chemoradiotherapy and radiotherapy in larynx preservation, and S1 combined radiotherapy, concurrent chemoradiotherapy and Tegafur Uracil combined radiotherapy showed superiority over radiotherapy in overall survival. In nonsurgical approaches, proper case selection is the key to success and may be much more important than pursuing radiotherapy dose escalation. In the analysis of surgical options, laser and supracricoid laryngectomy with cricohyoidoepiglottopexy contributed to larynx preservation in early- and intermediate-stage cancers, respectively. Supracricoid laryngectomy with cricohyoidoepiglottopexy demonstrated overall survival not worse than total laryngectomy, which is the prerequisite treatment basis for larynx preservation options. We must make extra efforts in pursuing an ideal balance between nonsurgical and surgical larynx preservation options.

Optimizing Organ Preservation Strategies through Chemotherapy-Based Selection in Esophageal Squamous Cell Carcinoma: Results from the CROC Multi-Institutional Phase II Clinical Trial.

PURPOSE: This study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Chemotherapy-naïve patients with resectable ESCC (stage IB-III, UICC, International Cancer Control 7th edition) were eligible for the study. All patients received three cycles of DCF therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1-5, repeated every three weeks). A remarkable response was defined as a reduction of the tumor to T1, metastatic lymph nodes smaller than 1 cm on the short axis, and downstaging to stage IA after three cycles of DCF therapy. Remarkable responders then underwent dCRT, which included two courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1-4, repeated every four weeks, along with 50.4 Gy of concurrent radiotherapy. The primary endpoint was 1-year progression-free survival (PFS) in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival (EFS). RESULTS: Of the 92 patients registered, 90 were analyzed. A remarkable response to three courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range: 1-85 months), the 1-year PFS was 89.8% (95% confidence interval = 77.2%-95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and EFS rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after two courses of DCF therapy was significantly associated with OS (p = 0.0049). CONCLUSIONS: In patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with three courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection.

Phase II study of concurrent chemoradiotherapy at the dose of 50.4 Gy with elective nodal irradiation for Stage II-III esophageal carcinoma.

OBJECTIVE: Definitive chemoradiotherapy is one of the curative options for resectable esophageal squamous cell carcinoma with organ preservation. We evaluated the efficacy and toxicity of radiotherapy at a dose of 50.4 Gy concurrent with chemotherapy for Stage II-III esophageal cancer. METHODS: Esophageal cancer patients with clinical Stage II-III (T1N1M0 or T2-3N0-1M0) were eligible. Radiotherapy was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Concurrent chemotherapy comprised two courses of 5-fluorouracil (1000 mg/m(2)/day) on days 1-4 and 2-h infusion of cisplatin (75 mg/m(2)) on Day 1; this was repeated every 4 weeks. Two courses of 5-fluorouracil with cisplatin were added. RESULTS: Fifty-one patients were enrolled in the study from June 2006 to May 2008. The characteristics of the 51 patients enrolled were as follows: median age 64 years; male/female, 45/6; performance status 0/1, 32/19 patients; Stage IIA/IIB/III, 9/20/22 patients, respectively. A complete response was achieved in 36 patients (70.6%). The 1- and 3-year overall survival rate was 88.2 and 63.8%, respectively. The median 1- and 3-year progression-free survival rate was 66.7% (80% CI: 57-74%) and 56.6% (80% CI: 47.1-64.9%), respectively. Acute toxicities included Grade 3/4 anorexia (45%), esophagitis (35%) and febrile neutropenia (20%). Eight patients (15.6%) underwent salvage surgery due to residual or recurrent disease. There were no deaths related to salvage surgery. CONCLUSION: Chemoradiation therapy at a dose of 50.4 Gy with elective nodal irradiation is promising with a manageable tolerability profile in esophageal cancer patients.

Salvage intensity modulated radiotherapy using endorectal balloon after radical prostatectomy: clinical outcomes.

OBJECTIVES: To evaluate biochemical non-evidence of disease and adverse events of salvage intensity-modulated radiotherapy using an endorectal balloon for prostate cancer patients after radical prostatectomy. METHODS: Data of 107 patients (median age 65 years) with persistent (>0.1 ng/mL) or rising prostate-specific antigen after radical prostatectomy were retrospectively analyzed. The mean dose to clinical target volume was 70 Gy in 32 fractions (the equivalent dose in 2 Gy fraction is 73.2 Gy based on α:ß = 2). Biochemical non-evidence of disease and predictive factors were assessed. Genitourinary toxicity and gastrointestinal toxicity were also evaluated using the Radiation Therapy Oncology Group toxicity criteria. RESULTS: The median follow up was 37 months (range 6-126 months). A total of 48 patients developed biochemical recurrence. The 3- and 5-year biochemical non-evidence of disease rates of all patients were 52.6% and 48.8%, respectively. The Gleason score (≥4 + 3, ≤3 + 4) and pre-intensity-modulated radiotherapy prostate-specific antigen level (≥0.5 ng/mL, <0.5 ng/mL) were significant predictive factors for biochemical non-evidence of disease in univariate analysis. In multivariate analysis, only the Gleason score was detected as a significant variable. The highest late genitourinary toxicities were grade 2 in 13% and grade 3 in 6% of patients. The highest late gastrointestinal toxicities were grade 2 in 6% and grade 3 in 3% of patients. CONCLUSION: Despite a relatively high radiation dose, intensity-modulated radiotherapy with an endorectal balloon can be delivered with acceptable toxicity and efficacy for patients developing biochemical recurrence after radical prostatectomy.

Dosimetric Predictors of Toxicity after Prostate Stereotactic Body Radiotherapy: A Single-Institutional Experience of 145 Patients.

The indications for stereotactic body radiotherapy (SBRT) for prostate cancer have increased. However, the relationships between adverse events and risk factors remain unclear. This study aimed to clarify associations between adverse events and dose index for prostate SBRT. Participants comprised 145 patients irradiated with 32-36 Gy in 4 fractions. Radiotherapy-related risk factors such as dose-volume histogram parameters and patient-related risk factors such as T stage and Gleason score were evaluated in a competing risk analysis. Median follow-up duration was 42.9 months. A total of 9.7% had acute Grade ≥ 2 GU toxicities and 4.8% had acute Grade ≥ 2 GI toxicities. A total of 11.1% had late Grade ≥ 2 GU toxicities and 7.6% had late Grade ≥ 2 GI toxicities. Two (1.4%) patients suffered from late Grade 3 GU toxicities. Similarly, two (1.4%) patients suffered from late Grade 3 GI toxicities. Acute GU and GI events correlated with prostate volume and dose to the hottest 10 cc volume (D10cc)/volumes receiving a minimum of 30 Gy (V30 Gy) of rectum, respectively. Late GI toxicity, frequency, and rectal hemorrhage correlated with rectal D0.1 cc/D1 cc, maximum dose to the bladder, and rectal D0.1 cc, respectively. Toxicities after prostate SBRT using 32-36 Gy/4 fractions were acceptable. Our analysis showed that acute toxicities correlated with volume receiving a medium dose level, and late toxicities correlated with highest point dose of organs at risk.

Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

Quality of life score as a prognosticator for pharyngeal cancer patients treated with radiotherapy.

The purpose of this study was to evaluate the prognostic value of quality of life (QOL) scores acquired not only pre-treatment, but also 1 month after treatment for locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with pharyngeal cancer treated using radiotherapy. Data for 102 patients with naso-, oro-, or hypo-pharyngeal cancer treated between December 2008 and September 2017 were retrospectively analyzed. About 90% of the patients were male. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was used for QOL assessments. Associations between QLQ-C30 scores before and 1 month after treatment and outcomes including LRC, DMFS, and OS were analyzed using Cox proportional hazard models. Median follow-up was 37 months (range, 5-117 months). Three-year LRC, DMFS, and OS rates were 77.8%, 60.0%, and 66.5%, respectively. Pre-treatment emotional functioning and diarrhea at 1 month after treatment were identified as significant predictors of LRC. Pre-treatment global QOL and diarrhea at 1 month after treatment were detected as significant predictors of DMFS. Pre-treatment emotional functioning, pre-treatment appetite loss, and diarrhea at 1 month after treatment were detected as significant predictors of OS. Diarrhea at 1 month after treatment was the most powerful QOL variable for predicting LRC, DMFS and OS. Our study revealed that several QOL scores not only before treatment but also 1 month after treatment correlated with LRC, DMFS and OS. In particular, the diarrhea domain of QOL at 1 month after treatment offered the most powerful prognosticator for pharyngeal cancer patients treated with radiotherapy.

Radiosensitization Effect of Gold Nanoparticles on Plasmid DNA Damage Induced by Therapeutic MV X-rays.

Gold nanoparticles (AuNPs) can be used with megavolt (MV) X-rays to exert radiosensitization effects, as demonstrated in cell survival assays and mouse experiments. However, the detailed mechanisms are not clear; besides physical dose enhancement, several chemical and biological processes have been proposed. Reducing the AuNP concentration while achieving sufficient enhancement is necessary for the clinical application of AuNPs. Here, we used positively charged (+) AuNPs to determine the radiosensitization effects of AuNPs combined with MV X-rays on DNA damage in vitro. We examined the effect of low concentrations of AuNPs on DNA damage and reactive oxygen species (ROS) generation. DNA damage was promoted by 1.4 nm +AuNP with dose enhancement factors of 1.4 ± 0.2 for single-strand breaks and 1.2 ± 0.1 for double-strand breaks. +AuNPs combined with MV X-rays induced radiosensitization at the DNA level, indicating that the effects were physical and/or chemical. Although -AuNPs induced similar ROS levels, they did not cause considerable DNA damage. Thus, dose enhancement by low concentrations of +AuNPs may have occurred with the increase in the local +AuNP concentration around DNA or via DNA binding. +AuNPs showed stronger radiosensitization effects than -AuNPs. Combining +AuNPs with MV X-rays in radiation therapy may improve clinical outcomes.