Stereotactic radiosurgery for prostate cancer spine metastases: local control and fracture risk using a simultaneous integrated boost approach.

OBJECTIVE: Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases. METHODS: Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence. RESULTS: A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear. CONCLUSIONS: High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Efficacy and safety evaluation of combined therapies incorporating whole-brain radiotherapy in patients with brain metastases: a systematic review and meta-analysis.

BACKGROUND: Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases. METHODS: In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. RESULTS: Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits. CONCLUSION: WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.

Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients.

BACKGROUND: Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients. METHODS: We conducted a retrospective analysis of 308 patients with stage 0-III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes. RESULTS: The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1-2 skin reactions (91.6%). The most common late toxicity was grade 0-1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1-2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes. CONCLUSIONS: SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Dose-escalated Salvage Whole-pelvic Radiotherapy for Biochemical Recurrence After Radical Prostatectomy for High-risk Prostate Cancer.

Background/Aim: To investigate the institutional experience of dose-escalated salvage whole-pelvic radiotherapy (WPRT) with the simultaneous integrated boost (SIB) technique in patients with biochemical recurrence (BCR) after radical prostatectomy for high-risk prostate cancer. Patients and Methods: This retrospective study included 21 patients with BCR who received radical prostatectomy for high-risk prostate cancer and underwent salvage RT. Clinical target volume (CTV) of the whole pelvis (CTV56) included the prostate bed, common iliac, external iliac, internal iliac, and obturator lymph node regions. The boost CTV (CTV66) included the prostate bed. Planning target volumes (PTV) were generated by adding a margin of 6-8 mm to CTV (PTV56 and PTV66). Doses of 56.1 and 66 Gy in 33 fractions were delivered to PTV56 and PTV66, respectively. Results: The 5-year biochemical progression-free survival, overall survival, and cause-specific survival rates were 72%, 94%, and 94%, respectively. A grade 3 late genitourinary toxicity event of gross hematuria was observed in one patient (4%). Acute and late toxicities of grade ≥3, other than gross hematuria, were not observed in any patient. Conclusion: Dose-escalated salvage WPRT using the SIB technique provides appropriate tumor control without increasing the incident of significant toxicities.

Comparing different boost concepts and beam configurations for proton therapy of pancreatic cancer.

Background and Purpose: Interfractional geometrical and anatomical variations impact the accuracy of proton therapy for pancreatic cancer. This study investigated field-in-field (FIF) and simultaneous integrated boost (SIB) concepts for scanned proton therapy treatment with different beam configurations. Materials and Methods: Robustly optimized treatment plans for fifteen patients were generated using FIF and SIB techniques with two, three, and four beams. The prescribed dose in 20 fractions was 60 Gy(RBE) for the internal gross tumor volume (IGTV) and 46 Gy(RBE) for the internal clinical target volume. Verification computed tomography (vCT) scans was performed on treatment days 1, 7, and 16. Initial treatment plans were recalculated on the rigidly registered vCTs. V100% and D95% for targets and D2cm3 for the stomach and duodenum were evaluated. Robustness evaluations (range uncertainty of 3.5 %) were performed to evaluate the stomach and duodenum dose-volume parameters. Results: For all techniques, IGTV V100% and D95% decreased significantly when recalculating the dose on vCTs (p < 0.001). The median IGTV V100% and D95% over all vCTs ranged from 74.2 % to 90.2 % and 58.8 Gy(RBE) to 59.4 Gy(RBE), respectively. The FIF with two and three beams, and SIB with two beams maintained the highest IGTV V100% and D95%. In robustness evaluations, the ΔD2cm3 of stomach was highest in two beams plans, while the ΔD2cm3 of duodenum was highest in four beams plans, for both concepts. Conclusion: Target coverage decreased when recalculating on CTs at different time for both concepts. The FIF with three beams maintained the highest IGTV coverage while sparing normal organs the most.

Effect of simultaneous integrated boost concepts on photoneutron and distant out-of-field doses in VMAT for prostate cancer.

BACKGROUND: A simultaneous integrated boost (SIB) may result in increased out-of-field (DOOF) and photoneutron (HPN) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare DOOF and HPN in flattened (FLAT) and flattening filter-free (FFF) 6­MV and 10-MV VMAT treatment plans with and without SIB. METHODS: Eight groups of 30 VMAT plans for PCA with 6 MV or 10 MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on a slab-phantom and compared with respect to measured DOOF and HPN in 61.8 cm distance from the isocenter. The 6­ and 10-MV flattened VMAT plans with conventional fractionation (6- and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as a function of delivered monitor units (MU) and weighted equivalent square field size Aeq. Pearson's correlation coefficients between the presented quantities were determined. RESULTS: The SIB plans resulted in decreased HPN over an entire prostate RT treatment course (10-MV SIB vs. CONV -38.2%). Omission of the flattening filter yielded less HPN (10-MV CONV -17.2%; 10-MV SIB -22.5%). The SIB decreased DOOF likewise by 39% for all given scenarios, while the FFF mode reduced DOOF on average by 60%. A strong Pearson correlation was found between MU and HPN (r > 0.9) as well as DOOF (0.7 < r < 0.9). CONCLUSION: For a complete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6­MV SIB FFF-VMAT when considering photoneutron or OOF doses.

Extended nodal radiotherapy for prostate cancer relapse guided with [11C]-choline PET/CT: ten-year results in patients enrolled in a prospective trial.

AIMS: To report long-term outcomes of relapsed prostate cancer (PC) patients treated in a prospective single-arm study with extended-nodal radiotherapy (ENRT) and [11C]-choline positron emission tomography (PET)/computed tomography (CT)-guided simultaneous integrated boost (SIB) to positive lymph nodes (LNs). METHODS: From 12/2009 to 04/2015, 60 PC patients with biochemical relapse and positive LNs only were treated in this study. ENRT at a median total dose (TD) = 51.8 Gy/28 fr and PET/CT-guided SIB to positive LNs at a median TD = 65.5 Gy was prescribed. Median PSA at relapse was 2.3 (interquartile range, IQR:1.3-4.0) ng/ml. Median number of positive LNs: 2 (range: 1-18). Androgen deprivation therapy (ADT) was prescribed for 48 patients for a median of 30.7 (IQR: 18.5-43.1) months. RESULTS: Median follow-up from the end of salvage treatment was 121.8 (IQR: 116.1, 130.9) months; 3-, 5-, and 10-year BRFS were 45.0%, 36.0%, and 24.0%, respectively; DMFS: 67.9%, 57.2%, and 45.2%; CRFS: 62.9%, 53.9%, and 42.0%; and OS: 88.2%, 76.3%, and 47.9%, respectively. Castration resistance (p < 0.0001) and ≥ 6 positive LN (p = 0.0024) significantly influenced OS at multivariate analysis. Castration resistance (p < 0.0001 for both) influenced DMFS and CRFS in multivariate analysis. CONCLUSIONS: In PC relapsed patients treated with ENRT and [11C]-choline-PET/CT-guided SIB for positive LNs, with 10-year follow-up, a median Kaplan-Meier estimate CRFS of 67 months and OS of 110 months were obtained. These highly favorable results should be confirmed in a prospective, randomized trial.

Evolution of the Management of Brain Metastases: A Bibliometric Analysis.

A systematic review of the published literature was conducted to analyze the management evolution of brain metastases from different cancers. Using the keywords "brain metastasis", "brain metastases", "CNS metastasis", "CNS metastases", "phase III" AND/OR "Randomized Controlled Trial" (RCT), relevant articles were searched for on the SCOPUS database. A total of 1986 articles were retrieved, published over a 45-year period (1977-2022). Relevant articles were defined as clinical studies describing the treatment or prevention of brain metastases from any cancer. Articles on imaging, quality of life, cognitive impairment after treatment, or primary brain tumors were excluded. After a secondary analysis, reviewing the abstracts and/or full texts, 724 articles were found to be relevant. Publications significantly increased in the last 10 years. A total of 252 articles (34.8%) were published in 12 core journals, receiving 50% of the citations. The number of publications in Frontiers in Oncology, BMC Cancer, and Radiotherapy and Oncology have increased considerably over the last few years. There were 111 randomized controlled trials, 128 review articles, and 63 meta-analyses. Most randomized trials reported on brain metastases management from unselected tumors (49), lung cancer (47), or breast cancer (11). In the last 5 years (2017 to 2022), management of brain metastasis has moved on from WBRT, the use of chemotherapy, and radio-sensitization to three directions. First, Radiosurgery or Radiotherapy (SRS/SRT), or hippocampal-sparing WBRT is employed to reduce radiation toxicity. Second, it has moved to the use of novel agents, such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) and third, to the use of molecularly directed therapy such as TKIs, in asymptomatic low volume metastasis, obviating the need for WBRT.

Preoperative Intensified Chemoradiation with Intensity-Modulated Radiotherapy and Simultaneous Integrated Boost Combined with Capecitabine in Locally Advanced Rectal Cancer: Long-Term Outcomes of a Real-Life Multicenter Study.

BACKGROUND: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. PATIENTS AND METHODS: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. RESULTS: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3-4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3-77.4) and 85.9% (95% CI: 80.2-90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0-13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5-26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3-5 were significantly associated with worse PFS, OS and metastasis-free survival. CONCLUSIONS: Preoperative IMRT-SIB with the moderate dose intensification of 52.5-57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.

Adding simultaneous integrated boost to whole brain radiation therapy improved intracranial tumour control and minimize radiation-induced brain injury risk for the treatment of brain metastases.

BACKGROUND: Brain metastases (BMs) are the most frequent intracranial tumours associated with poor clinical outcomes. Radiotherapy is essential in the treatment of these tumours, although the optimal radiation strategy remains controversial. The present study aimed to assess whether whole brain radiation therapy with a simultaneous integrated boost (WBRT + SIB) provides any therapeutic benefit over WBRT alone. METHODS: We included and retrospectively analysed 82 patients who received WBRT + SIB and 83 who received WBRT alone between January 2012 and June 2021. Intracranial progression-free survival (PFS), local tumour control (LTC), overall survival (OS), and toxicity were compared between the groups. RESULTS: Compared to WBRT alone, WBRT + SIB improved intracranial LTC and PFS, especially in the lung cancer subgroup. Patients with high graded prognostic assessment score or well-controlled extracranial disease receiving WBRT + SIB had improved intracranial PFS and LTC. Moreover, WBRT + SIB also improved the long-term intracranial tumour control of small cell lung cancer patients. When evaluating toxicity, we found that WBRT + SIB might slightly increase the risk of radiation-induced brain injury, and that the risk increased with increasing dosage. However, low-dose WBRT + SIB had a tolerable radiation-induced brain injury risk, which was lower than that in the high-dose group, while it was comparable to that in the WBRT group. CONCLUSIONS: WBRT + SIB can be an efficient therapeutic option for patients with BMs, and is associated with improved intracranial LTC and PFS. Furthermore, low-dose WBRT + SIB (biologically effective dose [BED] ≤ 56 Gy) was recommended, based on the acceptable risk of radiation-induced brain injury and satisfactory tumour control. TRIAL REGISTRATION: Retrospectively registered.

Novel approach of prophylactic radiation to reduce toxicities comparing 2-step40 with 56-Gy simultaneous integrated boost intensity-modulated radiation therapy for locally advanced squamous cell carcinoma of the head and neck, an intergroup phase III trial (JCOG1912, NEW BRIDGE).

BACKGROUND: Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN. METHODS: This study is a multicenter, two-arm, open-label, randomized phase III trial. Patients with LA-SCCHN excluding p16 positive oropharynx cancer are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score. DISCUSSION: If the experimental arm is non-inferior to the standard arm in terms of TTF and superior on the safety endpoints, the 2-step40 procedure is the more useful treatment than SIB56 for definitive CRT. TRIAL REGISTRATION: This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100 ( https://jrct.niph.go.jp/latest-detail/jRCTs031210100 ). Date of Registration: May 2021.

Volumetric-Modulated Arc-Based Re-radiosurgery With Simultaneous Reduced-Dose Whole-Brain Irradiation for Local Failures Following Prior Radiosurgery of Brain Oligometastases From Small Cell Lung Cancer.

First-line and possibly repeated stereotactic radiosurgery (SRS) with preserving whole-brain radiotherapy (WBRT) is an attractive and promising option for synchronous or metachronous limited brain metastases (BMs) from small cell lung cancer (SCLC), for which a modest prescription dose is generally preferred, such as a biological effective dose of ≤60 Gy, based on the linear-quadratic formula with an alpha/beta ratio of 10 (BED10). In addition, the optimal planning scheme for re-SRS for local progression after SRS of BMs from SCLC remains unclear. Herein, we describe a case of limited BMs developing after a partial response to standard chemoradiotherapy (CRT) for limited-stage SCLC. The BMs, including local failures following prior single-fraction (fr) SRS, were re-treated with volumetric-modulated arc-based SRS combined with simultaneous reduced-dose WBRT. The first SRS with 36.3 Gy/3 fr (BED10 80 Gy) for a small BM resulted in a local control of 17.2 months. However, the second SRS with 20 Gy/1 fr (BED10 60 Gy) to the 60% or 85% isodose surface (IDS) covering the gross tumor volume (GTV) of three new BMs with a paradoxical T1/T2 mismatch, that is, a visible mass on T2 larger than an enhancing area, resulted in partial symptomatic local progression of all lesions within 5.2 months, along with the development of two new lesions, despite continued amrubicin monotherapy. In contrast, the third SRS with 53 Gy/10 fr (BED10 81 Gy) to ≤74% IDSs encompassing the GTV boundary resulted in complete responses of all the lesions during six months. However, despite a combined use of WBRT of 25 Gy in the third SRS, symptomatic spinal cerebrospinal fluid dissemination and new BMs developed, the former leading to patient mortality. A BED10 of ≥80 Gy to the GTV margin and a steep dose increase inside the GTV boundary are suitable to ensure excellent local control in SRS for SCLC BMs. Re-SRS with the aforementioned scheme can be an efficacious option for local failures following prior SRS with a BED10 of ≤60 Gy. Modest dose escalation with a simultaneous integrated boost to bulky lesions in the initial CRT may reduce the development of new BM through improved control of the potential source.

Choice of radiotherapy modality for the combined treatment of non-small cell lung cancer with brain metastases: whole-brain radiation therapy with simultaneous integrated boost or stereotactic radiosurgery.

Purpose: To compare Whole-brain radiation therapy with simultaneous integrated boost (WBRT+SIB) to stereotactic radiosurgery (SRS)for non-small cell lung cancer (NSCLC)with brain metastases (BMs)in terms of overall survival (OS), intracranial progression-free-survival(iPFS), toxicity and objective response rate (ORR). Methods: A retrospective review was performed in our hospital of 90 patients diagnosed with NSCLC- BM who received either SRS (n = 48) or WBRT+SIB (n = 42) from January 2016 to January 2022. 76 (84.44%) patients received systemic drug therapy after radiotherapy, including chemotherapy(n=53), targeted therapy(n=40), immunotherapy(n=23), and anti-vascular drug therapy(n=45). OS and iPFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate and Multivariate analysis of the prognostic factors was performed using the Cox proportional hazard regression model. Results: The WBRT+SIB cohort had a longer median iPFS (20.0 versus (VS) 12.0 months, P = 0.0069) and a similar median OS (32.0 vs 28.0 months, P = 0.195) than the SRS cohort. Intracranial objective response rates in WBRT +SIB and SRS cohorts were 76.19% and 70.09%, respectively (P = 0.566). Disease control rates were 88.09% and 83.33%, respectively (P = 0.521). Multivariate analysis showed that WBRT+SIB is the only factor affecting iPFS(hazard ratio (HR):0.597 {95%confidence interval(CI):0.370-0.966}, P=0.035). Sex, Liver metastasis and Lymph node metastasis are risk factors for NSCLC-BM. Conclusion: In the context of systemic drug therapy, WBRT+SIB may have better intracranial local control than SRS in NSCLC-BM patients.

Dosimetric comparison between RapidArc and HyperArc in hippocampal-sparing whole-brain radiotherapy with a simultaneous integrated boost.

The HyperArc technique is known for generating high-quality radiosurgical treatment plans for intracranial lesions or hippocampal-sparing whole-brain radiotherapy (WBRT). However, there is no reported feasibility of using the HyperArc technique in hippocampal-sparing WBRT with a simultaneous integrated boost (SIB). This study aimed to compare dosimetric parameters of 2 commercially-available volumetric-modulated arc radiotherapy techniques, HyperArc and RapidArc, when using hippocampal-sparing WBRT with a SIB to treat brain metastases. Treatment plans using HyperArc and RapidArc techniques were generated retrospectively for 19 previously treated patients (1 to 3 brain metastases). The planning target volumes for the whole brain (excluding the hippocampal avoidance region; PTVWB) and metastases (PTVmet) were prescribed 25 and 45 Gy, respectively, in 10 fractions. Each plan included homogeneous and inhomogeneous delivery to the PTVmet. Dosimetric parameters for the target (conformity index [CI], homogeneity index [HI], target coverage [D95%]), and nontarget organs at risk were compared for the HyperArc and RapidArc plans. For homogeneous delivery, dosimetric parameters, including mean CI, HI, and target coverage in PTVWB and PTVmet, were superior for HyperArc than RapidArc plans (all p < 0.01). The PTVWB and PTVmet target coverage for HyperArc plans was significantly greater than for RapidArc plans (96.17% vs 93.38%, p < 0.01; 94.02% vs 92.21%, p < 0.01, respectively). HyperArc plans had significantly lower mean hippocampal Dmax and Dmin values than RapidArc plans (Dmax: 15.53 Gy vs, 16.71 Gy, p < 0.01; Dmin: 8.33 Gy vs 8.93 Gy, p < 0.01, respectively). Similarly, inhomogeneous delivery of hyperArc produced a superior target and lower hippocampal dosimetric parameters than RapidArc, except for the HI of PTVmet (all p < 0.01). HyperArc generated superior conformity and target coverage with lower hippocampal doses than RapidArc. HyperArc could be an attractive technique for hippocampal-sparing WBRT with an SIB.

Simultaneous Integrated Boost for Dose Escalation in Node-Positive Cervical Cancer: 5-Year Experience in a Single Institution.

This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who received definitive chemoradiotherapy by VMAT 45 Gy in 25 fractions with SIB to 55-57.5 Gy, followed by magnetic resonance image-guided adaptive brachytherapy (IGABT) between 2018 and 2022 were identified. A standardized strategy regarding nodal boost delivery and elective para-aortic (PAO) irradiation was employed. Primary endpoints were involved nodal control (INC) and regional nodal control (RNC). Secondary endpoints were pelvic control (PC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), failure pattern, and radiotherapy-related toxicities. A total of 234 involved nodes (182 pelvic and 52 PAO) in 54 patients, with a median of 3 involved nodes per patient (range 1-16), were analyzed. After a median follow-up of 19.6 months, excellent INC was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial RNC, PC, LRC, DFS, and OS were 93%, 87%, 87%, 78%, and 85%, respectively. Adenocarcinoma histology was associated with worse RNC (p = 0.02) and OS (p = 0.04), whereas the primary tumor maximum standardized uptake value (SUVmax) was associated with worse PC (p = 0.04) and LRC (p = 0.046) on univariate analysis. The incidence of grade ≥3 acute and late radiotherapy-related toxicity were 2% and 4%, respectively. Treatment of node-positive LACC with VMAT with SIB allows safe and effective dose escalation. The 5-year local experience demonstrated excellent treatment outcomes without additional toxicity.

Simultaneous vs. Sequential Boost for Adjuvant Breast Radiotherapy.

BACKGROUND/AIM: During the last 10-15 years, alternative regimens for adjuvant radiotherapy (RT) of breast cancer have become more popular, including simultaneous integrated (SIB) instead of sequential boosts (SEB). We present long-term outcomes after conventional fractionation (CF) plus SIB vs. CF+SEB. PATIENTS AND METHODS: Forty-eight patients receiving CF+SIB (treatment time=5.5 weeks) were matched to 72 patients (control group) receiving CF+SEB (6.5 weeks) considering twelve characteristics. Both groups were compared for radiation dermatitis, pneumonitis, local control (LC), metastases-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Rates of grade ≥2 dermatitis were 35.4% (CF+SIB) and 45.8% (CF+SEB), respectively (p=0.26), and rates of grade ≥2 pneumonitis 0% and 4.2%, respectively (p=0.27). Six-year LC, MFS, CSS, and OS rates were 100% vs. 93% (p=0.11), 97% vs. 100% (p=0.29), 100% vs. 100% (p=1.00), and 98% vs. 100% (p=0.23), respectively. CONCLUSION: CF+SIB was similar to CF+SEB in terms of toxicities and outcomes but reduces total treatment time by one week.

Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image guided-IMRT in locally advanced rectal cancers.

Purpose: To analyse the safety and efficacy of neoadjuvant chemoradiation (NACRT) with dose-escalated image-guided intensity modulated radiation therapy (IG-IMRT) in locally advanced (T3/4; T1-4N1-2) rectal cancers (LARCs). Materials and methods: Twenty patients with the diagnosis of LARC were recruited in this prospective interventional single-arm study treated by IG-IMRT with 45 Gray (Gy) in 25 fractions to elective nodal volumes and 55 Gy in 25 fractions to the gross primary and nodal disease with concurrent capecitabine 825 mg/m2 twice daily on radiotherapy days. Patients underwent total mesorectal excision 6-8 weeks post completion of NACRT followed by adjuvant chemotherapy (Capecitabine and oxaliplatin every 3 weekly for 6-8 cycles). Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Clinical T stage was T3:T4 in 19:1 and clinical N0:N1: N2 in 2:7:11 patients, respectively. With a median follow up of 21.2 months (13.8-25.6 months), 18 of 20 (90%) patients received the full course of treatment. Tumour and nodal downstaging was achieved in 78% and 84% of patients, respectively. pCR and overall complete response (defined as pCR and near CR) was achieved in 22.2% and 44.4% of patients, respectively. 2 (10%) patients completed NACRT, and achieved complete clinical response but refused surgery. Adjuvant chemotherapy course was completed by 17/18 (94.5%) patients. Grade 3 toxicities were observed in 2 (10%) patients during NACRT. All patients were disease-free at the time of the last follow up. Conclusion: Dose-escalation of NACRT therapy with IG-IMRT in LARC patients offers decent rates of pCR and overall response with excellent LRC and acceptable toxicities.

[Adjuvant radiation therapy for breast cancer]. / Adjuvante Strahlentherapie des Mammakarzinoms.

Adjuvant radiotherapy is an integral part of multimodal therapy for early breast cancer. It contributes to the reduction of local recurrences across all disease stages. (Moderate) hypofractionated whole-breast irradiation is the standard of care. In low-risk situations, partial breast irradiation can be an option. The indication for adjuvant radiotherapy after mastectomy or additional irradiation of regional lymph nodes depends on the patient's individual risk profile. Long-term results of treatment and further development of irradiation techniques now allow shorter, individualized and well-tolerated treatments with the aim of therapy de-escalation.

Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. METHODS: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). RESULTS: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). CONCLUSIONS: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.