DiffuseRT: predicting likely anatomical deformations of patients undergoing radiotherapy.

Predicting potential deformations of patients can improve radiotherapy treatment planning. Here, we introduce new deep-learning models that predict likely anatomical changes during radiotherapy for head and neck cancer patients. Denoising diffusion probabilistic models (DDPMs) were developed to generate fraction-specific anatomical changes based on a reference cone-beam CT (CBCT), the fraction number and treatment dose. Three distinct DDPMs were developed: (1) the image model was trained to directly generate likely future CBCTs, (2) the deformable vector field (DVF) model was trained to generate DVFs that deform a reference CBCT and (3) the hybrid model was trained similarly to the DVF model, but without relying on an external deformable registration algorithm. The models were trained on 9 patients with longitudinal CBCT images (224 CBCTs) and evaluated on 5 patients (152 CBCTs). The generated images mainly exhibited random positioning shifts and small anatomical changes for early fractions. For later fractions, all models predicted weight losses in accordance with the training data. The distributions of volume and position changes of the body, esophagus, and parotids generated with the image and hybrid models were more similar to the ground truth distribution than the DVF model, evident from the lower Wasserstein distance achieved with the image (0.26) and hybrid model (0.25) compared to the DVF model (0.36). Generating several images for the same fraction did not yield the expected variability since the ground truth anatomical changes were only in 70% of the fractions within the 95% bounds predicted with the best model. Using the generated images for robust optimization of simplified proton therapy plans improved the worst-case clinical target volume V95 with 7% compared to optimizing with 3 mm set-up robustness while maintaining a similar integral dose. In conclusion, the newly developed DDPMs generate distributions similar to the real anatomical changes and have the potential to be used for robust anatomical optimization.

Are we making progress in curing advanced cervical cancer-again?

Major improvements in radiotherapy over the past two decades in the definitive treatment of locally advanced cervical cancer have significantly improved loco-regional control and survival, whereas little progress has been made with chemotherapy since the implementation of concomitant cisplatin 25 years ago. However, the randomized study INTERLACE (A phase III multicenter trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with locally advanced cervical cancer) of neoadjuvant chemotherapy presented recently, has shown significant improvement in survival with the use of six cycles of weekly carboplatin and paclitaxel. Although INTERLACE is yet to be published, neoadjuvant chemotherapy is already being advocated as the new standard, and studies are being designed with neoadjuvant chemotherapy followed by chemoradiation and brachytherapy as the standard arm. It is noteworthy that INTERLACE was initiated before the improvements in radiotherapy mentioned above were broadly implemented. The survival rate in the standard arm of INTERLACE was therefore inferior to the results obtained with the latest state-of-the-art external beam radiotherapy and image guided adaptive brachytherapy (EMBRACE, Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer). Moreover, patient selection impedes the comparison of INTERLACE with other studies as the patients included in INTERLACE were younger, had better performance status, and had less advanced disease than in other studies. Notably patients with involved para-aortic nodes were excluded. In this review, we discuss neoadjuvant chemotherapy in the frame of the EMBRACE studies and show how the impact of modern radiotherapy and patient selection affects the interpretation of the results of INTERLACE. This has led us to conclude that neoadjuvant chemotherapy is not needed for the majority of patients with cervical cancer treated with definitive modern radiotherapy, and may cause harm. However, it is possible that short course neoadjuvant chemotherapy may benefit a minor subgroup of patients who need to be identified. Comprehensive understanding, including cost utility analyses, are needed to draw conclusions regarding the potential benefit of neoadjuvant chemotherapy in low and middle income countries with limited access to modern radiotherapy.

Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14).

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for Adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). The recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with 5 of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in 5 patients (5.4%) and 4 cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in 2 patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion: BCS followed by PORT was the predominant treatment approach for ACC of the breast and local recurrence mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Molecular separation-assisted label-free SERS combined with machine learning for nasopharyngeal cancer screening and radiotherapy resistance prediction.

Nasopharyngeal cancer (NPC) is a malignant tumor with high prevalence in Southeast Asia and highly invasive and metastatic characteristics. Radiotherapy is the primary strategy for NPC treatment, however there is still lack of effect method for predicting the radioresistance that is the main reason for treatment failure. Herein, the molecular profiles of patient plasma from NPC with radiotherapy sensitivity and resistance groups as well as healthy group, respectively, were explored by label-free surface enhanced Raman spectroscopy (SERS) based on surface plasmon resonance for the first time. Especially, the components with different molecular weight sizes were analyzed via the separation process, helping to avoid the possible missing of diagnostic information due to the competitive adsorption. Following that, robust machine learning algorithm based on principal component analysis and linear discriminant analysis (PCA-LDA) was employed to extract the feature of blood-SERS data and establish an effective predictive model with the accuracy of 96.7% for identifying the radiotherapy resistance subjects from sensitivity ones, and 100% for identifying the NPC subjects from healthy ones. This work demonstrates the potential of molecular separation-assisted label-free SERS combined with machine learning for NPC screening and treatment strategy guidance in clinical scenario.

Natural Guardians: Natural Compounds as Radioprotectors in Cancer Therapy.

Cancer remains a significant global health challenge, with millions of deaths attributed to it annually. Radiotherapy, a cornerstone in cancer treatment, aims to destroy cancer cells while minimizing harm to healthy tissues. However, the harmful effects of irradiation on normal cells present a formidable obstacle. To mitigate these effects, researchers have explored using radioprotectors and mitigators, including natural compounds derived from secondary plant metabolites. This review outlines the diverse classes of natural compounds, elucidating their roles as protectants of healthy cells. Furthermore, the review highlights the potential of these compounds as radioprotective agents capable of enhancing the body's resilience to radiation therapy. By integrating natural radioprotectors into cancer treatment regimens, clinicians may improve therapeutic outcomes while minimizing the adverse effects on healthy tissues. Ongoing research in this area holds promise for developing complementary strategies to optimize radiotherapy efficacy and enhance patient quality of life.

A systematic review and meta-analysis informing the role of adjuvant radiotherapy (RT) in Grade 2 and 3 oligodendroglioma.

BACKGROUND AND PURPOSE: Evidence and clinical guidelines support the use of adjuvant RT in high-risk low-grade gliomas. However, patients with oligodendroglioma have a more indolent disease course and delaying or avoiding RT is often considered to reduce treatment-related toxicities. As the optimal adjuvant management for oligodendroglioma is unclear, we aimed to assess the effect of adjuvant RT on overall survival (OS) and progression-free survival (PFS). METHODS: MEDLINE, EMBASE, CENTRAL and CINAHL were searched from January 1990 to February 2023 for studies comparing adjuvant RT versus no adjuvant RT for patients with oligodendroglioma. RESULTS: This review found 17 eligible studies including 14 comparative retrospective studies and 3 randomized controlled trials. Using random-effects model, the results suggested that adjuvant RT improved OS by 28 % (HR 0.72, 95 % CI (0.56-0.93), I2 = 86 %), and PFS by 48 % (HR 0.52, (95 % CI 0.40-0.66), I2 = 48 %) compared to patients without adjuvant RT. Subgroup analysis showed that upfront adjuvant RT improved OS and PFS compared to salvage RT. There were no significant differences in OS and PFS between adjuvant RT versus adjuvant chemotherapy. There was improvement in PFS but not OS for adjuvant chemoradiotherapy versus adjuvant chemotherapy alone. Adjuvant RT improved OS in WHO Grade 3 but not WHO Grade 2 oligodendroglioma. CONCLUSION: Overall, adjuvant RT improved OS and PFS in patients with oligodendroglioma. In patients with low-risk features (e.g. Grade 2, gross total resection), alternative approaches and individualization of management such as adjuvant chemotherapy alone may be reasonable considering the lack of survival benefit. Future efforts should prospectively investigate these treatment regimens on molecularly-classified oligodendroglioma patients (defined by presence of IDH mutation and 1p/19q co-deletion), balancing between maximizing survival outcomes and reducing RT-related toxicities.

Mathematical analysis of FLASH effect models based on theoretical hypotheses.

OBJECTIVE: Clinical applications of FLASH radiotherapy require formulas to describe how the FLASH radiation features and other related factors determine the FLASH effect. Mathematical analysis of the models can connect the theoretical hypotheses with the radiobiological effect, which provides the foundation for establishing clinical application models. Moreover, experimental and clinical data can be used to explore the key factors through mathematical analysis. Approach: We abstract the complex models of the oxygen depletion hypothesis and radical recombination-antioxidants hypothesis into concise mathematical equations. The equations are solved to analyze how the radiation features and other factors influence the FLASH effect. Then we propose methodologies for determining the parameters in the models and utilizing the models to predict the FLASH effect. Main results: The formulas linking the physical, chemical and biological factors to the FLASH effect are obtained through mathematical derivation of the equation. The analysis indicates that the initial oxygen concentration, radiolytic oxygen consumption and oxygen recovery are key factors for the oxygen depletion hypothesis and that the level of antioxidants is the key factor for the radical recombination-antioxidants hypothesis. According to the model derivations and analysis, the methodologies for determining parameters and predicting the FLASH effect are proposed: the criteria for data filtration; the strategy of hybrid FLASH and conventional dose rate (CONV) irradiation to ensure the acquisition of effective experimental data across a wide dose range; pipelines of fitting parameters and predicting the FLASH effect. Significance: This study establishes the quantitative relationship between the FLASH effect and key factors. The derived formulas can be used to calculate the FLASH effect in future clinical FLASH radiotherapy. The proposed methodologies guide to obtain sufficient high-quality datasets and utilize them to predict FLASH effect. Furthermore, this study indicates the key factors of FLASH effect and offers clues to further explore the FLASH mechanism.

Effectiveness of mHealth intervention for trismus exercise in patients with head and neck cancer undergoing proton and heavy ion therapy: a randomized control trial.

PURPOSE: This study aimed to compare the effects of a mobile health intervention based on social cognitive theory with standard care on maximal mouth opening, exercise compliance, and self-efficacy in patients receiving proton and heavy ion therapy for head and neck cancer. METHODS: This open-label, parallel-group, randomized, superiority trial involved a self-developed "Health Enjoy System" intervention. We assessed maximal mouth opening, exercise compliance, and self-efficacy at baseline (T0), post-treatment (T1), and at 1 month (T2) and 3 months (T3) after radiotherapy. Generalized estimating equations were used to analyze differences between the groups over time, with results reported as P values and 95% confidence intervals (CIs). RESULTS: The study included 44 participants. At T3, the intervention group showed a 6 mm greater increase in maximal interincisal opening than the control group (mean difference = 6.0, 95% CI = 2.4 to 9.5, P = 0.001). There was also a significant difference in exercise compliance between the groups (mean difference = 31.7, 95% CI = 4.6 to 58.8, P = 0.022). However, no significant difference in self-efficacy was found between the groups. CONCLUSION: This study demonstrated that an mHealth intervention incorporating behavior change theory could effectively enhance or maintain maximal mouth opening in patients undergoing proton and heavy ion therapy for head and neck cancer in China. This approach provides valuable support during and after treatment. TRIAL REGISTRATION: ChiCTR: ChiCTR2300067550. Registered 11 Jan 2023.

18F-FDG PET/CT- and MRI-Based Locally Advanced Cervical Cancer Early-Response Assessment after Concurrent Chemo- and Radiotherapy-Impact on Patient Outcomes and Survival Prediction.

With one third of patients with locally advanced cervical cancer (LACC) expected to develop cancer recurrence in the first two years after therapy, accurate assessment of the response and timely detection of cancer recurrence after concurrent chemo- and radiotherapy (CCRT) treatment is of great importance. Although there is neither definite consensus about the preferred imaging modality, nor the time interval until the first diagnostic examination after CCRT, the National Comprehensive Cancer Network (NCCN) recommends the use of MRI and 18F-FDG PET/CT as a post-treatment LACC response-assessment imaging tools. In this study, we tried to appraise the early therapy response in LACC patients by both 18F-FDG PET/CT and MRI in regard to the follow-up imaging results and their mutual interrelationship, and to ascertain if the post-treatment 18F-FDG PET/CT and MRI results were related to the progression-free and overall survival rate in women with LACC after CCRT. We also aimed to estimate the early and follow-up diagnostic imaging impact on further therapy management. Based on our results, we concluded that 18F-FDG PET/CT did surpass MRI in the early assessment of therapeutic response in LACC patients after CCRT. Both modalities provided information that may serve as predictive biomarkers of outcome and LACC patients' survival.

Exploring Extravasation in Cancer Patients.

Extravasation, the unintended leakage of intravenously administered substances, poses significant challenges in cancer treatment, particularly during chemotherapy and radiotherapy. This comprehensive review explores the pathophysiology, incidence, risk factors, clinical presentation, diagnosis, prevention strategies, management approaches, complications, and long-term effects of extravasation in cancer patients. It also outlines future directions and research opportunities, including identifying gaps in the current knowledge and proposing areas for further investigation in extravasation prevention and management. Emerging technologies and therapies with the potential to improve extravasation prevention and management in both chemotherapy and radiotherapy are highlighted. Such innovations include advanced vein visualization technologies, smart catheters, targeted drug delivery systems, novel topical treatments, and artificial intelligence-based image analysis. By addressing these aspects, this review not only provides healthcare professionals with insights to enhance patient safety and optimize clinical practice but also underscores the importance of ongoing research and innovation in improving outcomes for cancer patients experiencing extravasation events.

High Rates of Organ Preservation in Rectal Cancer with Papillon Contact X-ray Radiotherapy: Results from a Swiss Cohort.

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer.

Optimizing Choice of Skin Surrogates for Surface-Guided Stereotactic Body Radiotherapy of Lung Lesions Using Four-Dimensional Computed Tomography.

Image-guided radiotherapy supported by surface guidance can help to track lower lung lesions' respiratory motion while reducing a patient's exposure to ionizing radiation. However, it is not always clear how the skin's respiratory motion magnitude and its correlation with the lung lesion's respiratory motion vary between different skin regions of interest (ROI). Four-dimensional computed tomography (4DCT) images provide information on both the skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. An analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on the respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing a lower lung lobe lesion, as well as the respiratory motion correlations between the nine ROIs and the TS. The effects of gender and the adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between the ROIs in both the respiratory motion magnitudes and their correlations with the TS have been detected. An overall negative correlation between the ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between the adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. The respiratory magnitudes in regions without rib support tend to be larger for men than for women, but no differences in the ROI-to-TS correlation between sexes have been detected. The described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

Brain Metastases from Thyroid Carcinoma: Prognostic Factors and Outcomes.

Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable owing to lower survival rates among such patients compared to those without intracranial involvement. Many questions about their management remain unclear. The aim of the present study was to analyze the characteristics, treatment modalities, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, the data of 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of primary thyroid cancer and brain metastasis, and survival were analyzed. Among our patient cohort, the mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis, the mean age was found to be 64.8 ± 14.9 years. The histological types of primary thyroid cancer were identified as papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range: 0-180 months). Ten patients were identified as having a single intracranial lesion, and ten patients were found to have multiple lesions. Surgical resection was primarily performed in fifteen patients, and whole-brain radiotherapy, radiotherapy, or tyrosine kinase inhibitors were applied in the remaining five patients. The overall median survival time was 15 months after the diagnosis of BMs from TC (range: 1-252 months). Patients with thyroid cancer can develop brain metastasis even many years after the diagnosis of the primary tumor. The results of our study demonstrate increased overall survival in patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary carcinoma and those with follicular thyroid carcinoma.

The Current Position of Postoperative Radiotherapy for Salivary Gland Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. RESULTS: A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56-66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0-100%), 40% (0-77%), and 31% (0-75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89-94%), 89% (95% CI, 86-93%), and 84% (95% CI, 73-92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70-83%), 67% (95% CI, 60-74%), and 61% (95% CI, 55-67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79-88%), 75% (95% CI, 72-79%), and 68% (95% CI, 62-74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3-14%). CONCLUSION: PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted.

Incidence, Characteristics and Survival Rates of Bladder Cancer after Rectosigmoid Cancer Radiation.

BACKGROUND: Historical external beam radiation therapy (EBRT) for rectosigmoid cancer (RCa) predisposed patients to an increased risk of secondary bladder cancer (BCa). However, no contemporary radiotherapy studies are available. We addressed this knowledge gap. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), we identified non-metastatic RCa patients who either underwent radiotherapy (EBRT+) or did not (EBRT-). Cumulative incidence plots and multivariable competing risk regression models (CRR) were fitted to address rates of BCa after RCa. In the subgroup of BCa patients, the same methodology addressed BCa-specific mortality (BCSM) according to EBRT exposure status. RESULTS: Of the 188,658 non-metastatic RCa patients, 54,562 (29%) were EBRT+ vs. 134,096 (73%) who were EBRT-. In the cumulative incidence plots, the ten-year BCa rates were 0.7% in EBRT+ vs. 0.7% in EBRT- patients (p = 0.8). In the CRR, EBRT+ status was unrelated to BCa rates (multivariable HR: 1.1, p = 0.8). In the subgroup of 1416 patients with BCa after RCa, 443 (31%) were EBRT+ vs. 973 (69%) who were EBRT-. In the cumulative incidence plots, the ten-year BCSM rates were 10.6% in EBRT+ vs. 12.1% in EBRT- patients (p = 0.7). In the CRR, EBRT+ status was unrelated to subsequent BCSM rates (multivariable HR: 0.9, p = 0.9). CONCLUSION: Although historical EBRT for RCa predisposed patients to higher BCa rates, contemporary EBRT for RCa is not associated with increased subsequent BCa risk. Moreover, in patients with BCa after RCa, exposure to EBRT does not affect BCSM.

Total Neoadjuvant Therapy in Localized Pancreatic Cancer: Is More Better?

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its advanced stage upon diagnosis and limited treatment options. Surgical resection, the primary curative approach, often results in poor long-term survival rates, leading to the exploration of alternative strategies like neoadjuvant therapy (NAT) and total neoadjuvant therapy (TNT). While NAT aims to enhance resectability and overall survival, there appears to be potential for improvement, prompting consideration of alternative neoadjuvant strategies integrating full-dose chemotherapy (CT) and radiotherapy (RT) in TNT approaches. TNT integrates chemotherapy and radiotherapy prior to surgery, potentially improving margin-negative resection rates and enabling curative resection for locally advanced cases. The lingering question: is more always better? This article categorizes TNT strategies into six main groups based on radiotherapy (RT) techniques: (1) conventional chemoradiotherapy (CRT), (2) the Dutch PREOPANC approach, (3) hypofractionated ablative intensity-modulated radiotherapy (HFA-IMRT), and stereotactic body radiotherapy (SBRT) techniques, which further divide into (4) non-ablative SBRT, (5) nearly ablative SBRT, and (6) adaptive ablative SBRT. A comprehensive analysis of the literature on TNT is provided for both borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), with detailed sections for each.

New Frontiers in the Treatment of Patients with HER2+ Cancer and Brain Metastases: Is Radiotherapy Always Useful?

Brain metastases (BM) pose a significant challenge in the management of HER2+ breast cancer since almost 50% of patients with HER2+ breast cancer develop brain tumors. The complex process of brain metastases involves genetic mutations, adaptations and mechanisms to overcome the blood-brain barrier. While radiotherapy is still fundamental in local therapy, its use is associated with cognitive adverse effects and limited long-term control, necessitating the exploration of alternative treatments. Targeted therapies, including tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates, offer promising options for HER2+ breast cancer patients with BM. Clinical trials have demonstrated the efficacy of these agents in controlling tumor growth and improving patient outcomes, posing the question of whether radiotherapy is always the unique choice in treating this cancer. Ongoing research into novel anti-HER2 antibodies and innovative combination therapies holds promise for advancing treatment outcomes and enhancing patient care in this clinical scenario. This narrative review provides a comprehensive overview of traditional medical treatments, molecularly targeted therapy and investigational agents in the management of HER2+ breast cancer with BM, highlighting the evolving landscape and potential future directions in treatment strategies to improve patient survival and quality of life.

Jasminum grandiflorum oral gel as an add-on to standard of care in radiation induced grade 2 oral mucositis - an open label pilot clinical trial.

BACKGROUND: Radiation-induced oral mucositis is one of the most critical dose-limiting toxicities associated with radiation therapy for oral cancer which can result in treatment interruption and compromise the quality of the life of cancer patients. Jati (Jasminum grandiflorum) is used in Ayurveda to treat oral conditions like stomatitis and mouth ulcers. OBJECTIVE: To test the feasibility of Jati oral gel as an add on therapy in grade 2 radiation-induced oral mucositis. MATERIALS AND METHODS: A prospective, open-label, non-randomised pilot trial was conducted on 20 patients with grade 2 radiation-induced oral mucositis at a tertiary cancer hospital. The control group received sodium bicarbonate mouthwash 4-5 times daily as the standard of care, while the intervention arm also received Jati oral gel twice daily. We used the ImageJ software for objective assessment and the Visual Analogue Scale for subjective pain assessment. The study was continued for 15 days or until the mucositis progressed to grade 3 or resolved to grade 1. RESULT: There was a significant reduction in the mean pain score and mean area of mucositis in the intervention group compared to the control group. CONCLUSION: Jati oral gel is a suitable medicament as an add-on therapy in managing grade 2 radiation-induced oral mucositis.

Ameliorative effect of nano-pregabalin in gastrocnemius muscle of gamma irradiated rats with an experimental model of fibromyalgia: Crosstalk of Sirt3, IL-1ß and PARP1 pathways.

BACKGROUND: Fibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation. METHODS: Gamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles. RESULTS: N-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1ß and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection. CONCLUSION: This study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.

"Mid-P strategy" versus "internal target volume strategy in locally advanced non small cell lung cancer: Clinical results from the randomized non-comparative phase II study Mid-P.

BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) reported poor 5-year survival rates with frequent local or regional recurrences. Personalized RT may contribute to improve control and clinical outcome. We investigated efficacy and tolerance of "Mid-position" (Mid-P) strategy versus the conventional Internal Target Volume (ITV) strategy in LA-NSCLC patients treated by definitive conformal radiotherapy. METHODS: This prospective non-comparative randomized monocentric phase II trial included adult patients with non-resected, non-metastatic, non-previously irradiated proven LA-NSCLC treated with definitive normo-fractionated conformal radiotherapy (+/- chemotherapy). Allocated patients (randomisation 2:1) were treated using Mid-P or ITV strategy. A Fleming single-stage design (1-sided α = 0.1, 80 % power, P0 = 30 %, P1 = 50 %) planned enrolment of 36 patients in the Mid-P group. The ITV group ensured the absence of selection bias. The primary outcome was 1-year progression-free- survival (1y-PFS) rate. RESULTS: Among 54 eligible patients included from September 2012 to May 2018, 51 patients were analyzed (Mid-P: N = 34; ITV: 17). The 1y-PFS was 38 % (1-sided 95 %CI 25 %-not reached) with Mid-P strategy, and 47 % (95 %CI [27 %-not reached[) with ITV. Loco-regional failure as first event mainly occurred within radiation-field regardless the strategy. Acute and middle-term radiation toxicities were observed with both strategies. CONCLUSION: Local control and survival remain poor using the Mid-P strategy in this prospective randomized non-comparative monocentric study investigating Mid-P strategy versus ITV strategy in LA-NSCLC. Since the Mid-P strategy is not integrated into routine software, and perceived as a time-consuming method, Mid-P strategy cannot be recommended in LA-NSCLCC treated by definitive normo-fractionated conformal radiotherapy outside clinical trials.