Total body irradiation versus thiotepa/busulfan-based conditioning regimens for myeloablative allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia.

Total body irradiation (TBI)-based conditioning regimens are generally recommended for allogeneic HSCT (allo-HSCT) in patients with acute lymphoblastic leukemia (ALL). Recent evidence suggests that modern chemotherapy-based regimens may be as effective. This multicenter retrospective study compared the clinical outcomes of myeloablative allo-HSCT with thiotepa, busulfan, and cyclophosphamide/fludarabine (TTB) to TBI-based conditioning. Between 2002 to 2018, 63 and 114 patients received TTB- and TBI-based conditioning regimens, respectively. The 5-year cumulative incidence of relapse was lower in the TBI cohort compared to the TTB cohort (30% [95% CI, 22-38] versus 47% [95% CI, 36-59]; P = 0.03). Multivariate analysis identified T-ALL, Ph-negative B-ALL, and measurable residual disease associated with a higher relapse risk. The 5-year cumulative incidence of non-relapsed mortality (NRM) was significantly lower with TTB (12% [95% CI, 5-20]) compared to TBI (25% [95% CI, 18-33]) (P = 0.001). Multivariate analysis found TBI conditioning, older age, and advanced stages of ALL at transplantation associated with a higher NRM. No statistical difference was seen in overall survival (49% [95% CI, 40-58] and 46% [95% CI, 35-60]) in the TBI and TTB groups, respectively; P = 0.9). The study suggests that TTB-based conditioning may be a promising option for ALL patients undergoing allo-HSCT, as it resulted in similar OS and lower NRM than TBI-based conditioning.

Clinical outcomes and timing on the combination of focal radiation therapy and immunotherapy for the treatment of brain metastases.

Introduction: Radiotherapy is one of the standard treatments for brain metastases (BM). Over the past years, the introduction of immunotherapy as routine treatment for solid tumors has forced investigators to review and evaluate how it would interact with radiation. Radiation and Immunotherapy have shown a synergic effect activating the host's immune system and enhancing treatment response. The combinatory effect on BM is currently under investigation. Methods: Data published on Pubmed to determine toxicity, survival, treatment characteristics and timing on the combination of radiotherapy and immunotherapy for the treatment of BM has been reviewed. Results: Mostly retrospective reviews report an improvement of intracranial progression free survival (iPFS) when combining radioimmunotherapy for BM patients. Two systematic reviews and meta-analysis and one phase II prospective trial also report a benefit on iPFS without an increase of toxicity. Among the published literature, the definition of concurrency is heterogeneous, being one month or even narrowed intervals correlated to better clinical outcomes. Toxicity due to concurrent radioimmunotherapy, specifically symptomatic radionecrosis, is also directly analyzed and reported to be low, similar to the toxicity rates secondary to stereotactic radiosurgery alone. Conclusion: Radiation combined with immunotherapy has shown in predominantly retrospective reviews a synergic effect on the treatment of BM. The concurrent combination of radioimmunotherapy is a feasible therapeutic strategy and seems to improve clinical outcomes, especially iPFS, when delivered within <30 days. Larger prospective and randomized studies are needed to establish reliable outcomes, best delivery strategies and toxicity profile.

Hypofractionated whole breast irradiation in association with hypofractionated or normofractionated boost to the tumor bed in early breast cancer: tolerance and efficacy analysis

Background The boost to the tumor bed improves local control in breast cancer and it is an important part of the breast conserving therapy. However, information about the use of a hypofractionated boost is sparse, thus further studies are needed. We conducted a retrospective study with the aim of comparing hypofractionated boost (HB) and normofractionated boost (NB) on skin toxicity and local control. Materials and methods A total of 96 women with early breast cancer undergoing breast-conserving surgery and hypofractionated whole breast irradiation (WBI) were retrospectively analyzed divided into hypofractionated boost group and conventional fractionation boost group. Forty-nine patients were treated with NB with 16 Gy in 8 fractions and 47 patients were treated with HB with 13.35 Gy in 5 fractions. We examined acute and chronic toxicity with CTCAE version 5. Results The median follow-up was 49.5 months (26–67). Median age was 57 years (36–82). Sixty-six patients (68.7%) were younger than 60 years at the time of boost and 30 (31.2%) were older than 60 years who received the boost due to poor prognostic factors. No differences were found between the two groups in terms of patient, tumor or treatment characteristics. Grade 2 acute skin toxicity was 6.3% in the NB group and 4.2% in the HB group. Chronic skin induration was 4.2% in the NB group and 1% in the HB group. They did not show grade 3 skin toxicity. There were also no differences in acute or late skin toxicity between the two groups. No local recurrences were evidenced. Conclusions Hypofractionated WBI associated with HB treatment is a viable option in the management of conservative breast therapy given the good tolerance and similar local control (AU)

Vaginal dilator use more than 9 months is a main prognostic factor for reducing G2 late vaginal complications in 3D vaginal cuff brachytherapy (interventional radiotherapy) ?

Purpose Analyse the impact of different prognostic factors on G2-late vaginal complications after vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) in postoperative endometrial cancer (PEC). Methods One hundred and twenty-six PEC patients treated with VBT ± EBRT were retrospectively analysed considering age, body mass index, applicator diameter, clinical target volume (CTV), use of dilators, chemotherapy and EQD2(α/β=3) at the most exposed 2 cm3 of the CTV as prognostic factors for vaginal complications. Late vaginal complications were evaluated using objective LENT-SOMA criteria. Statistics: descriptive analysis, Chi-square, Fisher and Student tests were applied. Univariate and multivariate analyses were performed with the Baptista–Pike exact method and multiple logistic regression. Results Mean age was 65 years (SD ± 10), and median follow-up was 66 months (8–104). 19/126 patients (15%) showed G2-late vaginal complications, and 107/126 (85%) G0–G1. Univariate analysis showed: CTV ≤ 9 cm3 (p = 0.036), use of dilators < 9 months (p = 0.015), and total ≥ 68 Gy EQD2 received by 2 cm3 of CTV (p = 0.039) were associated with G2-late vaginal toxicity. Multivariate analysis showed the use of dilators < 9 months as an independent prognostic factor for G2-late vaginal toxicity (p = 0.043, OR 8.59, CI 1.59–159.9). Conclusion The use of dilators < 9 months in VBT ± EBRT for PEC was an independent prognostic factor for G2-late vaginal toxicity. The use of vaginal dilators ≥ 9 months requires further analysis in studies evaluating late vaginal toxicity (AU)

Hypofractionated whole breast irradiation in association with hypofractionated or normofractionated boost to the tumor bed in early breast cancer: tolerance and efficacy analysis.

BACKGROUND: The boost to the tumor bed improves local control in breast cancer and it is an important part of the breast conserving therapy. However, information about the use of a hypofractionated boost is sparse, thus further studies are needed. We conducted a retrospective study with the aim of comparing hypofractionated boost (HB) and normofractionated boost (NB) on skin toxicity and local control. MATERIALS AND METHODS: A total of 96 women with early breast cancer undergoing breast-conserving surgery and hypofractionated whole breast irradiation (WBI) were retrospectively analyzed divided into hypofractionated boost group and conventional fractionation boost group. Forty-nine patients were treated with NB with 16 Gy in 8 fractions and 47 patients were treated with HB with 13.35 Gy in 5 fractions. We examined acute and chronic toxicity with CTCAE version 5. RESULTS: The median follow-up was 49.5 months (26-67). Median age was 57 years (36-82). Sixty-six patients (68.7%) were younger than 60 years at the time of boost and 30 (31.2%) were older than 60 years who received the boost due to poor prognostic factors. No differences were found between the two groups in terms of patient, tumor or treatment characteristics. Grade 2 acute skin toxicity was 6.3% in the NB group and 4.2% in the HB group. Chronic skin induration was 4.2% in the NB group and 1% in the HB group. They did not show grade 3 skin toxicity. There were also no differences in acute or late skin toxicity between the two groups. No local recurrences were evidenced. CONCLUSIONS: Hypofractionated WBI associated with HB treatment is a viable option in the management of conservative breast therapy given the good tolerance and similar local control.

Vaginal dilator use more than 9 months is a main prognostic factor for reducing G2­late vaginal complications in 3D­vaginal­cuff brachytherapy (interventional radiotherapy)?

PURPOSE: Analyse the impact of different prognostic factors on G2-late vaginal complications after vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) in postoperative endometrial cancer (PEC). METHODS: One hundred and twenty-six PEC patients treated with VBT ± EBRT were retrospectively analysed considering age, body mass index, applicator diameter, clinical target volume (CTV), use of dilators, chemotherapy and EQD2(α/ß=3) at the most exposed 2 cm3 of the CTV as prognostic factors for vaginal complications. Late vaginal complications were evaluated using objective LENT-SOMA criteria. STATISTICS: descriptive analysis, Chi-square, Fisher and Student tests were applied. Univariate and multivariate analyses were performed with the Baptista-Pike exact method and multiple logistic regression. RESULTS: Mean age was 65 years (SD ± 10), and median follow-up was 66 months (8-104). 19/126 patients (15%) showed G2-late vaginal complications, and 107/126 (85%) G0-G1. Univariate analysis showed: CTV ≤ 9 cm3 (p = 0.036), use of dilators < 9 months (p = 0.015), and total ≥ 68 Gy EQD2 received by 2 cm3 of CTV (p = 0.039) were associated with G2-late vaginal toxicity. Multivariate analysis showed the use of dilators < 9 months as an independent prognostic factor for G2-late vaginal toxicity (p = 0.043, OR 8.59, CI 1.59-159.9). CONCLUSION: The use of dilators < 9 months in VBT ± EBRT for PEC was an independent prognostic factor for G2-late vaginal toxicity. The use of vaginal dilators ≥ 9 months requires further analysis in studies evaluating late vaginal toxicity.

Why is a very easy, useful, old technique underused? An overview of esophageal brachytherapy - interventional radiotherapy.

Endoesophageal brachytherapy (EBT) or endoesofageal interventional radiotherapy (EIRT) is an effective technique that has been used with varying frequency for many years. It is a very good technique in T1-T2 inoperable esophageal cancer and in the palliation of dysphagia. However, only some centers have access to this technique, and consequently, it is underused. Here, we discussed the indications and several technical aspects as well as the literature available. Also, why this technique is underused and how this can be overcome. We consider that EBT is a very effective technique that should be used whenever indicated.

Rectal neuroendocrine carcinoma: case report of a rare entity and perspective review of promising agents.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumours, which can be classified into neuroendocrine tumours (NETs), neuroendocrine carcinomas (NECs) and mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs). To date, there is no consensus regarding the optimal therapy, which usually depends on the primary location and classification, according to morphological features of differentiation and proliferation rates. Nevertheless, multidisciplinary strategies combining medical treatments and locoregional strategies have yielded better efficacy results. Here, we report the case of a patient diagnosed with a nonfunctional rectal NECs with metastatic widespread to pelvic lymph nodes and bilateral lung metastases. The patient received three cycles of platinum-etoposide, concomitantly with palliative radiotherapy. Although CT scan after three cycles showed a significant partial response, there was an early fatal progression only 3 months after having stopped systemic therapy. As formerly described in the literature, this case highlights the aggressive behaviour of NECs, rare tumours that often present in advanced stages at diagnosis. Lately, new insights into the molecular biology of NECs have unveiled the possibility of using novel drugs, such as targeted agents or immunotherapy, in molecularly selected subgroups of patients. In this review, we discuss the current management of this rare entity and provide an overview of the most relevant molecular findings, whilst illustrating the potential value that prescreening panels can offer, searching for actionable targets (MSI/dMMR, PD-L1, BRAFv600E) to guide therapy with promising agents that could fill a void in this disease.