Stereotactic body radiation therapy for low and intermediate risk prostate cancer—Results from a multi-institutional clinical trial

BackgroundWe report the outcome of a phase I/II clinical trial of stereotactic body radiation therapy (SBRT) for low (LR) and select intermediate risk (IR) prostate cancer (PCa) patients.Patients and methodsEligible patients included men with prostate adenocarcinoma with Gleason score 6 with PSA ≤ 20 or Gleason 7 with PSA ≤ 15 and clinical stage ≤ T2b. For the phase I portion of the study patients in cohorts of 15 received 45, 47.5, or 50 Gray (Gy) in five fractions. Since the maximally tolerated dose was not met in the phase I study, an additional 47 patients received 50 Gy in five fractions in the phase II study. Toxicity using Common Toxicity Criteria for Adverse Events v. 3.0, quality of life, and outcome data was collected.ResultsA total of 91 patients are included for analysis; 63.7% had NCCN IR and 36.3% had LR PCa. At a median follow up of 54 months the actuarial freedom from biochemical failure was 100% at 3 years and 98.6% at 5 years. Actuarial distant metastasis free survival was 100% at 3 and 5 years. Overall survival was 94% at 3 years and 89.7% at 5 years with no deaths attributed to PCa. Acute and late urinary grade ≥ III toxicity occurred in 0% and 5.5% of patients, respectively. Gastrointestinal (GI) acute and late toxicity of grade ≥ III occurred in 2% and 7% of patients, respectively. A total of four men experienced grade IV toxicity (three GI, one genitourinary).ConclusionSBRT treatment results in excellent biochemical control rates at 5 years for LR and IR PCa patients although doses greater than 47.5 Gy in five fractions led to increased severe late toxicity.     

局限期前列腺癌大分割调强放疗临床Ⅱ期研究

目的 观察前列腺癌2.7 Gy 25次大分割调强适形放疗的疗效和不良反应。     

High-dose-rate brachytherapy in uterine cervical carcinoma

PURPOSE: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. METHODS AND MATERIALS: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. RESULTS: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for Stage I, 76.52% for Stage II, and 50.4% for Stage III patients. Local failure occurred in 2 (11.1%) of the 18 Group 1 patients and in 20 (21.0%) of the 95 Group 2 patients. Distant failure occurred in none of the Group 1 patients and in 8 (8.4%) of the 95 Group 2 patients. None of the patients developed Grade 3 rectal toxicity. Grade 3 bladder toxicity was observed in 2 patients. The actuarial risk of Grade 3 or worse late toxicity was 3.31%. CONCLUSION: The results of our study indicate that HDR brachytherapy at 9 Gy/fraction is both safe and effective in the management of carcinoma of the cervix, with good local control and a minimum of normal tissue toxicity.     

Advancements in the radiooncological Treatment of High-risk Prostate Cancer: A Quarter Century of Achievements

BackgroundThe aim of the study was to evaluate the development of treatment of primary high-risk prostate cancer in regards to biochemical no evidence of disease (bNED), acute and late gastrointestinal (GI) and genitourinary (GU) side effects.Patients and methodsPrimary high-risk prostate cancer patients treated between 1994 and 2016 were included. Applied doses ranged from 60 to 80 Gy, with a dose of 1.8 or 2 Gy per fraction. Techniques were either 3D conformal or intensity modulated radiotherapy and volumetric intensity modulated arc therapy.Results142 patients were treated with doses up to 70 Gy (median dose 66 Gy; 66 Gy group), 282 with doses between 70 and 76 Gy (median dose 74 Gy; 74 Gy group), and 141 with doses >76 Gy (median dose 78 Gy; 78 Gy group). The median follow-up was 48 months. The bNED rates were 50% after 5 years and 44% after 9 years in the 66 Gy group; 65% and 54%, respectively, in the 74 Gy group; and 83% and 66%, respectively, in the 78 Gy group (p = 0.03 vs. 74 Gy and p < 0.0001 vs. 66 Gy). We found a higher rate of acute GI side effects in the 78 Gy group compared to the other groups, but not in maximum acute GU side effects and late maximum GI and GU effects.ConclusionsHigh-risk prostate cancer patients treated with doses of 78 Gy had significantly better bNED rates. Compared to the historical 66 Gy group, 50% more patients achieved bNED after a follow-up of 9 years.Key words: biochemical control, gastrointestinal toxicity, genitourinary toxicity, dose escalation     

Toxicity of high-dose radiotherapy combined with daily cisplatin in non-small cell lung cancer: results of the EORTC 08912 phase I/II study. European Organization for Research and Treatment of Cancer

The purpose of this work was to study the feasibility of concurrent chemoradiation in patients with inoperable non-small cell lung cancer (NSCLC). 40 patients with inoperable NSCLC were treated with escalating doses of radiotherapy and cisplatin (cDDP). The radiation dose was increased step by step from 60.5 to 66 Gy in daily fractions of 2.75 Gy. Chemotherapy was also increased step by step from 20 to 24 daily doses of cDDP 6 mg/m(2) and given concurrently with radiotherapy. A dose of 40 Gy/2 Gy/20 fractions (fx) was given to the EPTV (elective planning target volume) which included the gross tumour volume with a margin of 2 cm and part of or the entire mediastinum. During each session a boost dose of 0.75 Gy was given simultaneously to the BPTV (boost planning target volume), which encompassed the GTV (gross tumour volume) with a margin of 1 cm, for the first 20 fx, so the total dose to the tumour was 55 Gy. Cisplatin 6 mg/m(2) was given 1 h prior to radiotherapy at each fraction. From then on the dose of radiation to the BPTV and the dose of cDDP were increased step by step. In group I the BPTV was irradiated with two extra fractions of 2.75 Gy to a total dose of 60. 5 Gy without cDDP. In group II the same total dose of 60.5 Gy was given but the last two fractions were combined with cDDP. In group III four extra fractions of 2.75 Gy were given to the BPTV to a total dose of 66 Gy, only two of these fractions combined with cDDP. Finally, in group IV a total dose of 66 Gy was given in 24 fractions, all fractions combined with cDDP. All patients were planned by means of a CT-based conformal treatment planning. The maximal length of the oesophagus receiving >/=60.5 Gy was 11 cm. 40 patients were evaluable for acute and late toxicity and for survival. Acute toxicity grade >/=3 (common toxicity criteria, CTC) was rarely observed; nausea/vomiting in 3 patients (8%), leucopenia in 2 patients (5%), thrombocytopenia in 2 patients (5%), whilst 2 patients (5%) suffered from severe weight loss. Late side-effects (European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group, EORTC/RTOG) were: oesophageal toxicity >/=grade 3 in 2 patients (5%) and radiation pneumonitis grades 1 (3%) and 2 (3%) in 1 patient each. Overall actuarial 1- and 2-year survival was 53% and 40%, respectively. The 1- and 2-year local disease-free interval was 65% and 58% respectively. Radiotherapy at a dose of 66 Gy/2.75 Gy/24 fx combined with daily cDDP 6 mg/m(2) given over 5 weeks is feasible and results in a good local disease-free interval and a good survival rate. This treatment schedule is at present being tested as one of the two treatment arms of EORTC phase III study protocol 08972/22973.     

Long-Term Results of Moderate Hypofractionation to Prostate and Pelvic Nodes Plus Androgen Suppression in High-Risk Prostate Cancer

PurposeModerate hypofractionated radiation therapy (HypoRT) is an attractive alternative to conventionally fractionated radiation therapy for prostate cancer. However, most studies using HypoRT only included the prostate as the target volume. We report long-term outcomes of patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and HypoRT to the prostate and nodal areas with a simultaneous integrated boost technique.Methods and MaterialsPatients with localized, high-risk prostate cancer entered a prospective phase I/II study with a HypoRT regimen of 60 Gy/20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated radiation therapy with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT. Toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events v3. Outcomes rates were calculated by the actuarial method of Kaplan–Meier from the date of last radiation treatment until date of event.ResultsWe report on the first 105 patients treated between October 2010 and February 2014. Median follow-up was 74 months, with 97% of patients followed for more than 36 months. Median ADT duration was 18 months. The worst grade 2 or higher late gastrointestinal or genitourinary toxicity was seen in 7% and 9%, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rates of grade ≥2 gastrointestinal or genitourinary toxicity were 2% and 3%, respectively, with no residual grade ≥3 toxicity. The 5- and 7-year actuarial overall survival and relapse free survival were 91% and 85% and 87% and 81%, respectively.ConclusionsThe longest follow-up report of moderate HypoRT (plus ADT) to the prostate and pelvic nodes shows that this approach is feasible, well tolerated, and effective. It is convenient for patients and the health system. A larger randomized trial using this approach is warranted.     

Estimation of the Incidence of Late Bladder and Rectum Complications After High-Dose (70–78 Gy) Conformal Radiotherapy for Prostate Cancer,Using Dose–Volume Histograms

Purpose: To investigate whether Dose–Volume Histogram (DVH) parameters can be used to identify risk groups for developing late gastrointestinal (GI) and genitourinary (GU) complications after conformal radiotherapy for prostate cancer.Methods and Materials: DVH parameters were analyzed for 130 patients with localized prostate cancer, treated with conformal radiotherapy in a dose-escalating protocol (70–78 Gy, 2 Gy per fraction). The incidence of late (>6 months) GI and GU complications was classified using the RTOG/EORTC and the SOMA/LENT scoring system. In addition, GI complications were divided in nonsevere and severe (requiring one or more laser treatments or blood transfusions) rectal bleeding. The median follow-up time was 24 months. We investigated whether rectal and bladder wall volumes, irradiated to various dose levels, correlated with the observed actuarial incidences of GI and GU complications, using volume as a continuous variable. Subsequently, for each dose level in the DVH, the rectal wall volumes were dichotomized using different volumes as cutoff levels. The impact of the total radiation dose, and the maximum radiation dose in the rectal and bladder wall was analyzed as well.Results: The actuarial incidence at 2 years for GI complications ≥Grade II was 14% (RTOG/EORTC) or 20% (SOMA/LENT); for GU complications ≥Grade III 8% (RTOG/EORTC) or 21% (SOMA/LENT). Neither for GI complications ≥Grade II (RTOG/EORTC or SOMA/LENT), nor for GU complications ≥Grade III (RTOG/EORTC or SOMA/LENT), was a significant correlation found between any of the DVH parameters and the actuarial incidence of complications. For severe rectal bleeding (actuarial incidence at 2 years 3%), four consecutive volume cutoff levels were found, which significantly discriminated between high and low risk. A trend was observed that a total radiation dose ≥ 74 Gy (or a maximum radiation dose in the rectal wall >75 Gy) resulted in a higher incidence of severe rectal bleeding (p = 0.07).Conclusions: These data show that dose escalation up to 78 Gy, using a conformal technique, is feasible. However, these data have also demonstrated that the incidence of severe late rectal bleeding is increased above certain dose–volume thresholds.     

Acute Side Effects After Definitive Stereotactic Body Radiation Therapy (SBRT) for Patients with Clinically Localized Or Locally Advanced Prostate Cancer: a Single Institution Prospective Study

BackgroundThe aim of the study was to evaluate acute side effects after extremely hypofractionated intensity-modulated radiotherapy (IMRT) with stereotactic body radiation therapy (SBRT) for definitive treatment of prostate cancer patients.Patients and methodsBetween February 2018 and August 2019, 205 low-, intermediate- and high-risk prostate cancer patients were treated with SBRT using “CyberKnife M6” linear accelerator. In low-risk patients 7.5–8 Gy was delivered to the prostate gland by each fraction. For intermediate- and high-risk disease a dose of 7.5–8 Gy was delivered to the prostate and 6–6.5 Gy to the seminal vesicles by each fraction with a simultaneous integrated boost (SIB) technique. A total of 5 fractions (total dose 37.5–40 Gy) were given on every second working day. Acute radiotherapy-related genitourinary (GU) and gastrointestinal (GI) side effects were assessed using Radiation Therapy Oncology Group (RTOG) scoring system.ResultsOf the 205 patients (28 low-, 115 intermediate-, 62 high-risk) treated with SBRT, 203 (99%) completed the radiotherapy as planned. The duration of radiation therapy was 1 week and 3 days. The frequencies of acute radiotherapy-related side effects were as follows: GU grade 0 – 17.1%, grade I – 30.7%, grade II – 50.7%, grade III – 1.5%; and GI grade 0 – 62.4%, grade I–31.7%, grade II–5.9%, grade III–0%. None of the patients developed grade ≥ 4 acute toxicity.ConclusionsSBRT with a total dose of 37.5–40 Gy in 5 fractions appears to be a safe and well tolerated treatment option in patients with prostate cancer, associated with slight or moderate early side effects. Longer follow-up is needed to evaluate long-term toxicity and biochemical control.Key words: prostate cancer, stereotactic radiotherapy, CyberKnife, extreme hypofractionation     

Hypofractionated helical tomotherapy using 2.5–2.6 Gy daily fractions for localized prostate cancer

Background

The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer.

Materials and methods

We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system.

Results

Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49–87) and the median follow-up 11 months (range 7–40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively).

Conclusion

Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control.     

Adjuvant hypofractionated radiation therapy for breast cancer after conserving surgery

AimsTo evaluate the incidence of locoregional recurrence (LRR) and the cosmetic results in a group of patients with breast cancer treated with a hypofractionated schedule of adjuvant radiotherapy after conservative surgery.Materials and methodsIn total, 539 patients with pTis–pT1–pT2 breast cancer underwent radiotherapy treatment after conservative surgery at the University of Florence and at the Pistoia Hospital. The dose delivered was 44 Gy (2.75 Gy daily fraction). The tumour bed boost (10 Gy) was given by electrons.ResultsAt the time of the analysis, 1.8% of patients (10/539) had breast relapse. No patients developed nodal recurrence (supraclavicular, axillary and internal mammary nodes). The 3- and 5-year actuarial rates for LRR were 1.2% (±0.5% standard error) and 2.1% (±0.6% standard error), respectively. Considering the late toxicity, we found that 412 (76.4%) patients had grade 0 or grade 1 late toxicity, 113 patients (20.9%) had grade 2 late toxicity and 14 patients (2.5%) had grade 3 late toxicity. No patients developed grade 4 toxicity.ConclusionThis type of approach resulted in an effective treatment in terms of local control in patients with negative or one to three positive axillary nodes and negative surgical margins. Patients treated with a hypofractionated schedule showed very good cosmesis.     

Hypofractionated intensity-modulated arc therapy for lymph node metastasized prostate cancer: Early late toxicity and 3-year clinical outcome

Background and purpose

For patients with N1 prostate cancer (PCa) aggressive local therapies can be advocated. We evaluated clinical outcome, gastro-intestinal (GI) and genito-urinary (GU) toxicity after intensity modulated arc radiotherapy (IMAT) + androgen deprivation (AD) for N1 PCa.

Material and methods

Eighty patients with T1-4N1M0 PCa were treated with IMAT and 2–3 years of AD. A median dose of 69.3 Gy (normalized isoeffective dose at 2 Gy per fraction: 80 Gy [α/β = 3]) was prescribed in 25 fractions to the prostate. The pelvic lymph nodes received a minimal dose of 45 Gy. A simultaneous integrated boost to 72 Gy and 65 Gy was delivered to the intraprostatic lesion and/or pathologically enlarged lymph nodes, respectively.GI and GU toxicity was scored using the RTOG/RILIT and RTOG-SOMA/LENT-CTC toxicity scoring system respectively. Three-year actuarial risk of grade 2 and 3/4 GI–GU toxicity and biochemical and clinical relapse free survival (bRFS and cRFS) were calculated with Kaplan–Meier statistics.

Results

Median follow-up was 36 months. Three-year actuarial risk for late grade 3 and 2 GI toxicity is 8% and 20%, respectively. Three-year actuarial risk for late grade 3–4 and 2 GU toxicity was 6% and 34%, respectively. Actuarial 3-year bRFS and cRFS was 81% and 89%, respectively. Actuarial 3-year bRFS and cRFS was, respectively 26% and 32% lower for patients with cN1 disease when compared to patients with cN0 disease.

Conclusion

IMAT for N1 PCa offers good clinical outcome with moderate toxicity. Patients with cN1 disease have poorer outcome.     

Hypofractionated External Beam Radiotherapy to Boost the Prostate with ≥85 Gy/Equivalent Dose for Patients with Localised Disease at High Risk of Lymph Node Involvement: Feasibility,Tolerance and Outcome

AimsTo evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique.Materials and methodsBetween 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0–50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system.ResultsAll patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049).ConclusionsThe use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.     

Dose escalation using ultra-high dose IMRT in intermediate risk prostate cancer without androgen deprivation therapy: preliminary results of toxicity and biochemical control

Background

To investigate the feasibility of dose escalation (86 Gy at 2 Gy/fraction) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer without androgen deprivation therapy.

Methods

Patients with histologically proven adenocarcinoma of the prostate, intermediate prognostic category, were enrolled in this study. Early and late toxicity were scored according to the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0. Treatment outcome was stated in terms of biochemical failure, biopsy result and clinical failure.

Results

39 patients with a median follow-up of 71 months were analyzed. No patient experienced G3 or G4 acute gastrointestinal (GI) or genitourinary (GU) toxicity. G2 acute GI and GU toxicity were observed in 17 (44%) and 20 (51%) patients, respectively. Fourteen patients (36%) did not experience acute GI toxicity and 4 patients (10%) did not experience acute GU toxicity. G2 late GI bleeding occurred in 7 of 39 patients (18%). Both G3 and G4 late GI toxicity were seen only in one patient (2.5%). Two patients (5%) experienced G2 late GU toxicity, while G3 late GU toxicity occurred in 3 patients (8%). The 5-year actuarial freedom from biochemical failure (FFBF) was 87%. Thirty-four patients (87%) did not show biochemical relapse. Seventeen patients (44%) underwent biopsy two year after radiotherapy; of these only two were non-negative and both did not show evidence of biochemical disease.

Conclusions

IMRT treatment of patients with localized intermediate-risk prostate cancer at high dose levels without using androgen deprivation therapy (ADT) seems to give good disease control. Nevertheless, future trials should aim at further decreasing toxicity by exploiting image guidance techniques and by reducing the dose delivered at the interface between organs at risk and prostate.

     

Phase II feasibility study of high-dose radiotherapy for prostate cancer using proton boost therapy: first clinical trial of proton beam therapy for prostate cancer in Japan

OBJECTIVE: To assess the feasibility of high-dose radiotherapy for prostate cancer using proton boost therapy following photon radiotherapy. METHODS: The primary endpoint was acute grade 3 or greater genitourinary (GU) and gastrointestinal (GI) toxicities. The study included patients with clinical stage T1-3N0M0 prostate cancer. Radiotherapy consisted of 50 Gy/25 fx photon irradiation to the prostate and the bilateral seminal vesicles followed by proton boost of 26 Gy(E)/13 fx to the prostate alone. Hormonal therapy was allowed before and during the radiation therapy. RESULTS: Between January 2001 and January 2003, 30 patients were enrolled in this study. Acute grade 1/2 GU and GI toxicities were observed in 20/4 and 17/0 patients, respectively. With the median follow-up period of 30 months (range 20-45), late grade 1/2 GU and GI toxicities occurred in 2/3 and 8/3 patients, respectively. No grade 3 or greater acute or late toxicities were observed. All patients were alive, but six patients relapsed biochemically after 7-24 months. CONCLUSIONS: Proton boost therapy following photon radiotherapy for prostate cancer is feasible. To evaluate the efficacy and safety of proton beam therapy, a multi-institutional phase II trial is in progress in Japan.     

Dosimetric Predictors of Genitourinary Toxicity From a Phase I Trial of Prostate Bed Stereotactic Body Radiation Therapy

PurposeOur purpose was to analyze dose-volume parameters associated with genitourinary (GU) toxicity from a phase I clinical trial of prostate bed stereotactic body radiation therapy.Methods and MaterialsPatients were treated in escalating dose levels of 35, 40, and 45 Gy, over 5 fractions. Data from all 26 patients enrolled in the protocol were analyzed using multiple dose-volume cut points for multiple GU organs at risk. Univariate logistical regression and Fisher exact test were used to assess statistical significance associated with incidence of toxicity.ResultsThe median follow-up was 36 months for all patients. Acute GU toxicity was mild and resolved spontaneously. Eight out of 26 patients (30.7%) developed late GU toxicity of grade 2 or higher. Two patients developed grade 3 ureteral stenosis, 1 in the 35 Gy arm and the other in the 45 Gy arm. Three patients developed grade 2 or higher hematuria/cystitis, and 3 developed grade 2 or higher incontinence. Incidence of grade 3 ureteral stenosis was related to the absolute volume of bladder wall receiving greater than 20, 25, and 30 Gy (P < .01). Grade 2 cystitis and hematuria were related to the volume of bladder wall receiving 20 Gy less than 34% and 35 Gy less than 25% (18.8% vs 60% and 23.8% vs 80%, respectively, P < .05). Incontinence was related to mean urethral dose less than 35 Gy and 25 Gy (4.3% vs 66.7% and 0% vs 37.5%, respectively, P < .05) and volume of urethra receiving 35 Gy less than 24% (8.3% vs 50%, P < .05).ConclusionsThis is the first analysis to report dose-volume thresholds associated with late GU toxicity in patients receiving prostate bed stereotactic body radiation therapy. We recommend limiting the bladder wall receiving 25 Gy to less than 18 cubic centimeters to reduce the risk for late grade 3 ureteral stenosis.     

Locoregional control and toxicity following high-dose hypofractionated and accelerated palliative radiotherapy regimens in breast cancer

AimsFor patients with locally advanced primary/recurrent breast cancer, radiotherapy is an effective treatment for locoregional control. 36 Gy in 6 Gy once-weekly fractions is a commonly used schedule, but there are no data comparing local control and toxicity between 36 Gy delivered once-weekly versus accelerated schedules of multiple 6 Gy fractions per week. This retrospective study compared local control rates and acute and late toxicity in patients undergoing 30–36 Gy in 6 Gy fractions over 6 weeks versus more accelerated schedules over 2–3 weeks for an unresected breast cancer.Materials and methodsPatients who received 30–36 Gy in 6 Gy fractions to an unresected breast cancer ± involved lymph nodes between December 2011 and August 2020 were identified. Patients were grouped into once-weekly versus accelerated fractionation schedules. Response rates, local control and toxicity data were analysed.ResultsIn total, 109 patients were identified. The median follow-up duration was 46 months. Forty-seven patients (43%) received once-weekly fractions and 62 patients (57%) received accelerated fractionation schedules. There were no significant differences in baseline tumour characteristics between the groups. Eighty-seven per cent of patients had an objective (complete or partial) response (81% in the once-weekly group; 91% in the accelerated group). The median time to local progression was 23.5 months overall (95% confidence interval 17.8–29.2); 23.5 months (95% confidence interval 18.8–28.1) in the once-weekly group and 19.0 months (95% confidence interval 7.0–31.1) in the accelerated group (P = 0.99). Acute toxicity of any grade occurred in 75% of patients (76% in the once-weekly group; 74% in the accelerated group) and grade 3 toxicity occurred in 7% of patients (7% in the once-weekly group; 8% in the accelerated group). There were no associations between the groups and acute or late toxicity grade (P = 0.78 and P = 0.26, respectively), although one grade 4 late toxicity (skin radionecrosis) occurred in a patient who received five fractions a week and therefore this regimen is not recommended. Study limitations included a lack of statistical power analysis, the necessary grouping of all accelerated patients for analysis and a high rate of censored data.ConclusionThere were no apparent differences in response rate, time to local progression or toxicity between patients who received 30–36 Gy in 6 Gy fractions once-weekly compared with twice-weekly as palliative treatment for locally advanced breast cancer. This regimen appears to be a safe alternative and may be preferred by patients.     

Adaptive Radiotherapy for Carcinoma of the Urinary Bladder: Long-term Outcomes With Dose Escalation

AimsTo report long-term outcomes with dose-escalated, image-guided adaptive radiotherapy (ART) for bladder preservation in muscle-invasive bladder cancer (MIBC).Materials and methodsAll MIBC patients receiving bladder-preserving ART at our institute from 2009 to 2018 were analysed. For ART, three anisotropic planning target volumes (PTV) were concentrically grown around the simulation bladder volume. A library of intensity-modulated radiotherapy plans was created for each patient. A total dose of 64 Gy in 32 fractions to the entire bladder and 55 Gy to pelvic nodes was planned, with 68 Gy to the tumour bed (2 Gy equivalent dose = 68.7 Gy, α/β = 10) as simultaneous integrated boost for solitary tumours. The most appropriate PTV encompassing the bladder (‘plan-of-the-day’) was chosen daily using on-board megavoltage imaging. Neoadjuvant and concurrent chemotherapy was prescribed for medically fit patients.ResultsOf a total of 106 patients, most had T2 (68%) or T3 (19%) disease. Ninety-two patients (87%) completed 64 Gy to the whole bladder. Sixty-three patients (59%) received 68 Gy as tumour bed boost. Seventy-six per cent received concurrent weekly chemotherapy. At a median follow-up of 26 months, 3-year locoregional control, disease-free survival and overall survival were 74.3, 62.9 and 67.7%, respectively. Eighty-two per cent of patients retained disease-free bladder. Radiation Therapy Oncology Group grade III/IV acute genitourinary and gastrointestinal toxicities were 7.5% and 0%, respectively, and late genitourinary/gastrointestinal toxicities were 6.5% and 3.8%, respectively. Overall survival, disease-free survival, locoregional control and grade III/IV genitourinary/gastrointestinal toxicities did not differ significantly with dose escalation.ConclusionPlan-of-the-day ART is clinically safe and effective for bladder preservation and can be implemented in routine clinical practice. A high bladder preservation rate is achievable without compromising on survival or toxicities. Dose escalation does not seem to affect outcomes.