Rolando Maria D Angelillo

Background: CDK4/6 inhibitor plus ET is a standard treatment for advanced HR+ BC. This study evaluates the efficacy and safety of CDK4/6 inhibitors with concurrent RT (SBRT and non-SBRT) in terms of pain, analgesic therapy changes, toxicities, and net clinical benefit (NCB). Methods: BC patients with bone metastases treated with RT and CDK4/6 inhibitor in the prospective observational COMBART study were analyzed. Pain was measured with the NRS. The NCB was defined by pain reduction (NRS), toxicity, and treatment changes. Adverse events (AEs) were graded per CTCAE v5.0. Statistical tests included chi-square and t-test. Results: Forty patients were treated with CDK4/6 inhibitor (palbociclib 30.8%, ribociclib 51.3%, abemaciclib 17.9%) and RT (131 lesions; 100 SBRT, 31 non-SBRT). The mean NRS score dropped from 3.52 (pre-treatment) to 1.31 (post-treatment) (p < 0.001), with better outcomes for patients treated with moderate hypofractionation (58.6% vs. 39.9% pain relief, p = 0.016). Pain relief was independent of the type of CDK4/6 inhibitor used (p = NS). Analgesic reduction was most common with palbociclib (35.4%, p = 0.001). Eight toxicities (grade 1–2) were reported. The NCB was 0.6 overall, higher with non-SBRT (0.74 vs. 0.52). Conclusions: RT plus CDK4/6 inhibitor, especially with moderate hypofractionation, significantly reduced pain with manageable toxicity. Analgesic therapy can often continue without stopping CDK4/6 inhibitor.

Radiotherapy is a crucial cancer treatment that demands precise planning to balance tumor eradication and preservation of healthy tissue. Traditional treatment planning (TP) is iterative, time-consuming, and reliant on human expertise, which can potentially introduce variability and inefficiency. We propose a novel framework to transform a large multimodal foundation model (MLM) into an action model for TP using a few-shot reinforcement learning (RL) approach. Our method leverages the MLM's extensive pre-existing knowledge of physics, radiation, and anatomy, enhancing it through a few-shot learning process. This allows the model to iteratively improve treatment plans using a Monte Carlo simulator. Our results demonstrate that this method outperforms conventional RL-based approaches in both quality and efficiency, achieving higher reward scores and more optimal dose distributions in simulations on prostate cancer data. This proof-of-concept suggests a promising direction for integrating advanced AI models into clinical workflows, potentially enhancing the speed, quality, and standardization of radiotherapy treatment planning.

Background: Pancreatic cancer, with its poor prognosis, is frequently diagnosed in elderly patients who may be ineligible for surgery or chemoradiation due to age or comorbidities. Stereotactic body radiotherapy (SBRT) offers a targeted approach by delivering precise, high-dose radiation to a limited volume in few fractions. This study aims to evaluate the efficacy and safety of SBRT in elderly pancreatic cancer patients. Methods: Patients with pancreatic cancer received SBRT using Volumetric Modulated Arc Therapy in schedules of five dose fractions tailored to the tolerance of adjacent tissues. Progression-free survival (PFS), local progression-free survival (LPFS), metastasis-free survival (MFS) and overall survival (OS) were analysed. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Median follow-up was 9.5 months (range, 4–37.2 months). The 1-year, 2-year and 3-year LPFS rates were 88%, 73% and 54%, respectively (median not reached). Median PFS, MFS and OS were 29.6 months, 32.6 months, and 24.1 months, respectively. SBRT was well tolerated with acute and late toxicity rates of 6% and 9%, respectively. Conclusionsd: SBRT appears to be an effective and safe option for elderly pancreatic cancer patients, achieving high local control with minimal toxicity.

The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Background: This study aims to assess the benefit of a deep inspiration breath hold (DIBH) over the standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with the LAD dose. Methods: Patients with left-sided breast cancer undergoing whole breast radiotherapy with DIBH were analyzed. All patients included in the analysis had plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were used to identify the cut-off point of parameters to predict the LAD maximum dose > 10 Gy and LAD mean dose > 4 Gy, and the areas under the curve (AUCs) were computed. Post-test probability has been performed to evaluate the effect of parameters’ combination. Results: One hundred ninety-seven patients were analyzed. The LAD dose was significantly reduced in DIBH plans with the maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs. 4.8 Gy, p ≤ 0.001) and 28.1% (mean value 8.2 Gy vs. 12.8 Gy, p ≤ 0.001) in DIBH plans compared to FB plans. The strongest predictor of the LAD dose (maximum > 10 Gy and mean > 4 Gy) was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume (LAD Dmax > 10 Gy) and lung volume, heart volume, and breast separation (LAD Dmean > 4 Gy). Conclusion: The dosimetric advantage of DIBH is clear in all patients and DIBH should always be preferred.

Background: to assess the benefit of a deep inspiration breath hold (DIBH) over standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with LAD dose. Methods: We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH. All patients had both plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were performed to define the cut-off point of parameters to predict LAD maximum dose >10 Gy and LAD mean dose > 4 Gy. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results: One hundred ninety-seven patients were identified. LAD dose was significantly reduced in DIBH plans with maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs 4.8 Gy, p= 4 Gy was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume for LAD Dmax > 10 Gy and lung volume, heart volume and breast separation for LAD Dmean > 4 Gy. Conclusion: The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients.