Local Treatment Research Articles

Development of photodynamic therapy in treating oral diseases

The morbidity of oral disorders, including gingivitis, caries, endodontic-periodontal diseases, and oral cancer, is relatively high globally. Pathogenic cells are the root cause of many oral disorders, and oral therapies depend on eradicating them. Photodynamic therapy (PDT) has been established as a potential and non-invasive local adjuvant treatment for oral disorders. PDT consists of three essential components: photosensitizer (PS), a light source with a certain wavelength, and oxygen dissolved in the cells. These three components can interact to cause damage to proteins, lipids, nucleic acids, and other biological components within diseased tissues. Herein, we aimed to provide a detailed understanding of PDT and how it can treat oral diseases. Concerns about PDT and potential remedies are also a factor. PDT has been shown in numerous clinical studies to be an efficient supplementary therapy that can reduce pathogenic cells. The PDT has great potential for dental applications, including treating bacterial and fungal infections during root canal therapy and preventing oral cancer, potentially malignant disorders, periodontitis, dental caries, and peri-implant disorders. Although PDT has been promoted as having significant potential and utility in dentistry, more clinical research must be conducted before being used broadly.

Evaluating the Efficacy of Combined Intravaginal Estriol Therapy and Kegel Exercises in Managing Menopausal Atrophic Vulvovaginitis

Background: This is a prospective study. Atrophic vulvovaginitis (VVA), a prevalent condition resulting from estrogen deficiency after the menopause, is characterized by symptoms such as vaginal dryness, itching, burning, dyspareunia, and urinary discomfort. Standard treatment involves systemic estrogen replacement therapy (HRT) and localized estrogen treatments, such as estriol. However, many women with moderate-to-severe VVA may not fully benefit from estrogen therapy alone. Non-hormonal adjunctive treatments, such as pelvic floor exercises (e.g., Kegel exercises), are being explored to enhance clinical outcomes. Objectives: This study investigates the combined effect of local estriol therapy and Kegel exercises in improving VVA symptoms in postmenopausal women. Methods: Fifty postmenopausal women diagnosed with VVA were enrolled and divided into three severity groups: mild, moderate, and severe. All participants received estriol therapy (0.5 mg vaginal tablets daily for 10 days each month) for the first three months. Following this, Kegel exercises were introduced for an additional three-month period, alongside continued estriol therapy. Symptom improvement was evaluated after six months, with outcomes categorized as complete remission, partial remission, or no remission. Results: Significant improvements in symptom remission were observed, particularly in the moderate and severe groups. In the mild VVA group, 81.82% achieved complete remission with combined therapy compared to 68.18% with estriol alone. In the severe group, complete remission was observed in 40% of patients receiving combined therapy compared to 20% with estriol therapy alone. These findings suggest that Kegel exercises enhance the effectiveness of estriol by improving local blood circulation, which facilitates better estrogen absorption and distribution. Conclusions: The addition of Kegel exercises to local estriol therapy significantly improves symptom remission rates, especially in moderate and severe VVA cases. This approach offers a promising strategy for managing postmenopausal VVA, particularly in cases that do not fully respond to estrogen therapy alone.

Image-Based Monitoring of Thermal Ablation

Thermal therapy is a commonly used local treatment technique in clinical practice. Monitoring the treatment process is essential for ensuring its success. In this review, we analyze recent image-based methods for thermal therapy monitoring, focusing particularly on their feasibility for synchronous or immediate postoperative monitoring. This includes thermography and other techniques that track the physical changes in tissue during thermal ablation. Potential directions and challenges for further clinical applications are also summarized.

Benchmarking the Efficacy of Salvage Systemic Therapies for Recurrent Meningioma: A RANO Group Systematic Review and Meta-analysis to Guide Clinical Trial Design.

Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propose a "rate of probable interest" to inform future clinical trial design and development on behalf of the RANO meningioma group. PubMed, ClinicalTrials.gov, and ASCOpubs databases were screened for clinical trials evaluating the activity of systemic therapies for adults with recurrent meningiomas. The pooled progression-free survival at 6-months and 1-year (PFS-6 and PFS-1 year) values were calculated using the random effects technique with I-squared indices. The pooled PFS-6 and PFS-1 year rates for recurrent WHO grade 1 meningiomas were 43.6% (95% CI: 22.7-67.0%, I2=80%) and 21.7% (95% CI: 6.2-53.9%, I2=76%), and for grade 2-3 meningiomas, the PFS-6 was 38.0% (95% CI: 28.3-48.8%, I2=68%). In targeted therapy group, PFS-6 and PFS-1 year rates stood at 62.0% (I2=58%) and 49.0% (I2=63%) for grade 1, while for grade 2-3 tumors, the PFS-6 rate with targeted therapy and immunotherapy was 42.1% (I²=60%) and 46.0% (I²=0%), respectively. The benchmarks were set at 67% and 54% for PFS-6 and PFS-1 year for grade 1 tumors, and PFS-6 of 49% for grade 2-3 tumors. Several studies have reported outcomes in patients with recurrent meningiomas testing a variety of agents with modest, but variable and progressively increasing activity. In this context, we recommend new benchmarks for future trials to define efficacy of future investigational therapies.

New systemic treatment approach for primary lymphoma of the orbit and the ocular adnexa

Orbital lymphomas are the most frequently occurring malignant tumor entities in this region. They are less frequently also localized in the ocular adnexa and show ahigh entity-specific heterogeneity regarding the treatment and prognosis. This article gives an overview of the heterogeneity of symptoms of orbital lymphoma and lymphoma of the ocular adnexa and focuses on new systemic options for treatment of this disease. For this article a systematic search of the PubMed databank was carried out and the practical knowledge of the authors was taken into account. Orbital lymphoma and lymphoma of the ocular adnexa show ahigh variability in the clinical symptoms and therefore require acomprehensive ophthalmological examination of the affected patients. Histopathologically assisted diagnostics after an incisional biopsy are essential for the classification into the various lymphoma entities. This is necessary for developing and carrying out atargeted treatment concept consisting of local and systemic treatment modalities. Especially for the new systemic treatment approaches, in addition to the histopathological classification of the lymphoma entity it is also necessary to analyze the molecular features in order to efficiently implement the new highly specific medications. Finally, a close interdisciplinary cooperation of all disciplines involved is absolutely necessary for the best possible treatment, including ophthalmology, hemato-oncology, radiotherapy, radiology, pathology and psycho-oncology. Depending on the localization of the tumor, inclusion of otorhinolaryngology, oral and maxillofacial surgery and/or neurosurgery can be necessary.

Inhalable Metal-Organic Frameworks: A Promising Delivery Platform for Pulmonary Diseases Treatment.

Inhalation delivery, offering a direct pathway for administering drugs to the lungs in the form of dry powders or aerosols, stands out as an optimal approach for the localized treatment of pulmonary diseases. However, the intricate anatomical architecture of the lung often poses challenges in maintaining effective drug concentrations within the lungs over extended periods. This highlights the pressing need to develop rational inhalable drug delivery systems that can improve treatment outcomes for respiratory diseases. Metal-organic frameworks (MOFs) assembled from inorganic metal ions and organic ligands, characterized by customizable porous architecture and chemical composition, modifiable porosity, vast surface area, straightforward surface modification, and adjustable biocompatibility, have garnered extensive attention in the biomedical sphere. The introduction of MOFs into inhalation therapy represents a promising avenue to navigate past the hurdles associated with traditional inhalation methods. Therefore, this review summarizes the characteristics of inhalation delivery together with the latest advances, challenges, and opportunities in utilizing inhalable MOFs for treating lung diseases and discusses prospects in this field alongside the potential pathways for translating this strategy into clinic.

Tumor-Resident Intracellular Bacteria Scavenger Activated In Situ Vaccines for Potent Cancer Photoimmunotherapy.

In situ tumor vaccines, which utilize antigens generated during tumor treatment to stimulate a cancer patient's immune system, has become a potential field in cancer immunotherapy. However, due to the immunosuppressive tumor microenvironment (ITME), the generation of tumor antigens is always mild and not sufficient. Tumor-resident intracellular bacteria have been identified as a complete tumor microenvironment component to contribute to creating ITME. Herein, a tumor-resident intracellular bacteria scavenger is designed to induce enhanced antitumor photoimmunotherapy-driven in situ vaccines for treating hypoxic tumors. This scavenger is developed by integrating photosensitizer CyI and antibiotics Doxycycline (Doxy) into thermal-sensitive tumor-derived exosomes fused liposomes (ECDL). In vitro and in vivo results showed that ECDL could homologous target to cancer cells and restrict the respiration of mitochondrial to reduce tumor hypoxia, thus providing continuous oxygen to eliminate both tumor cells and tumor-resident intracellular bacteria, which could induce in situ vaccines for ablating the primary tumor and inhibiting the tumor metastasis and recurrence. Moreover, eliminating tumor-resident intracellular bacteria neutralizes the ITME and triggers the production of bacterial-related neoantigens, which could further strength the immunotherapy. This study provided versatile and effective in situ vaccines that are promising for local, abscopal, and metastatic tumor treatment.

Outcomes associated with local treatment of nasal planum squamous cell carcinoma in dogs: 89 cases (2003-2020).

To describe the clinical characteristics, treatments, complications, and outcomes in dogs with nasal planum squamous cell carcinoma (SCC) undergoing local treatment. A retrospective, multi-institutional study was performed. Medical records were searched to identify dogs diagnosed with nasal planum SCC. Variables were recorded from medical records and statistically analyzed. 89 dogs were included. The most common presenting complaint was a visible mass on the nasal planum (89%). Metastasis was detected in 12% of dogs at the time of local therapy. Local therapy consisted of surgical excision alone in 63 of 89 dogs (71%) and radiation therapy alone in 20 of 89 dogs (22%); 6 dogs had multiple local therapies. Tumor size decreased in 12 dogs (60%) undergoing radiation therapy alone. Local recurrence was reported in 19 of 89 dogs (21%), including 16 of 63 dogs (25%) treated with surgery alone. Median survival time of all dogs was 452 days (95% CI, 285 to 576). Median survival time among 33 dogs with documented disease progression was 336 days (95% CI, 189 to 458), versus 685 days (95% CI, 334 to 1,042) in 56 dogs that did not have documented disease progression, which was significantly different (P = .038). Documented disease progression was significantly associated with hazard of death (hazard ratio, 1.93; 95% CI, 1.03 to 3.63; P = .041). Dogs undergoing local treatment of nasal planum SCC had a favorable prognosis. Metastasis at the time of treatment was uncommon. Long-term survival was possible, particularly in cases without disease progression. Aggressive local therapy, particularly surgical resection, should be considered in dogs with nasal planum SCC.

Degradation Potential of Metakaolin-Based Geopolymer Composites Immersed in Real and Simulated Acidic Environments

This study investigates the degradation potential of metakaolin-based geopolymer (GP) composites when exposed to real and simulated acidic environments. Traditional OPC concrete, commonly used in wastewater treatment facilities, faces considerable deterioration due to the destructive chemical composition of municipal wastewater. This extensive investigation aims to assess the performance of GP composites as a sustainable alternative to such materials. The metakaolin-based GP mortar samples were prepared and subjected to immersion in a primary clarifier unit at a local wastewater treatment plant (real) and a laboratory-made acetic acid solution (simulation) for up to four weeks after curing. The analysis included measurements of % strength and % weight loss, as well as characterization techniques such as isothermal calorimetry, microstructure (SEM), and mercury porosimetry (MIP). The outcomes signified a cumulative heat generation of 534 J/g at three days, with an average compressive strength of 79.4 MPa past 28 days. Exposure to acetic acid led to a 13% decline in compressive strength and a 3.90% loss in sample weight, while exposure to real wastewater resulted in an 18% strength and a 5.60% weight loss. Observations from SEM revealed microstructural changes, including the formation of biofilms and air voids, indicating multifaceted interactions between the GP matrix and its surrounding environment. This research effectively highlights the potential of metakaolin-based geopolymer composites to improve durability against acidic conditions, suggesting future applications in the construction of infrastructure exposed to such harsh chemical environments.

Considerations to forgo systemic treatment in patients with advanced esophageal or gastric cancer: A real-world evidence study.

The majority of patients with advanced esophageal or gastric cancer do not start palliative systemic treatment. To gain insight into the considerations underlying the decision not to start systemic treatment, we analyzed characteristics of patients starting and not starting systemic treatment, reasons for not starting systemic treatment, and receipt of local palliative treatments on a nationwide scale. Patients diagnosed with advanced esophageal or gastric cancer between 2015 and 2021 were included (n = 10,948). Survival was compared using propensity score matching on patient and disease characteristics. Most patients did not start systemic treatment (esophageal cancer 59%; gastric cancer 64%). These patients were generally older, more often female, had more comorbidities and a worse performance status. The main reason for not starting systemic treatment was patient or family preference (35%). Among patients who did not start systemic treatment, 47% (esophageal) and 19% (gastric), received local palliative treatment, most commonly radiotherapy. Patients who did not start systemic treatment had worse median overall survival compared to patients who did start (esophageal cancer 2.9 months vs. 8.9 months; gastric cancer 2.2 vs. 8.2 months). These findings indicate that patient condition and disease burden are important aspects in systemic treatment decisions. However, patient or family preference was the main reason for not starting systemic treatment, highlighting that their priorities also strongly influence the decision. Systemic treatment did show to be associated with improved overall survival in matched patients, and therefore adequately weighing treatment risks and benefits based on real world data against patient preferences is of utmost importance.

Injectable Senolytic Hydrogel Depot for the Clearance of Senescent Cells.

Small molecules are frontline therapeutics for many diseases; however, they are often limited by their poor solubility. Therefore, hydrophobic small molecules are often encapsulated or prepared as pure drug nanoparticles. Navitoclax, used to eliminate senescent cells, is one such small molecule that faces challenges in translation due to its hydrophobicity and toxic side effects. Further, as senescent cells exhibit context-dependent pathologic or beneficial properties, it is preferable to eliminate senescent cells locally. To formulate navitoclax and enable local treatment, we designed an injectable hydrogel loaded with navitoclax nanoparticles as a senolytic delivery vehicle. Navitoclax nanoparticles (Ø ∼ 110 nm) were prepared via solvent-antisolvent nanoprecipitation and formulated in an injectable polymer-nanoparticle (PNP) hydrogel to create a local senolytic depot. Navitoclax-loaded PNP hydrogels selectively cleared senescent cells in vitro in senescent endothelial monolayers. This work demonstrates the value of formulating lipophilic small molecules and the potential of localized drug delivery strategies to improve senolytic therapies.

Endocrine dysfunction in long-term survivors of pediatric head and neck rhabdomyosarcoma.

Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy. Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study. The presence of any endocrine dysfunction was assessed cross-sectionally using Common Terminology Criteria of Adverse Events grading, anthropometrics, and biochemical testing. Retrospective chart review was added to this clinical assessment. Ninety-six survivors with long follow-up time (median, 9 years) were included. Any endocrinopathy was present in 35% of survivors, with 88% having pituitary, 6% peripheral (thyroid), and 6% combined insufficiencies. None had gonadal insufficiency. Growth hormone deficiency was diagnosed in 31 (32%) survivors, with additional pituitary insufficiencies in 12 (39%). In 8%, central precocious puberty preceded API. None of the survivors given brachytherapy had API. The prevalence of pituitary dysfunction in HNRMS survivors is high, emphasizing the importance of systematic endocrine assessment during follow-up, including pubertal development and growth. Efforts should be made to further reduce extraneous irradiation to endocrine organs to prevent dysfunction later in life.

Anti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV.

Alteration of visual acuity in wet age-related macular degeneration (AMD) is mostly driven by vascular endothelial growth factor A (VEGF-A)-induced edema from leaky newly forming blood vessels below the retina layers. To date, all therapies aimed at alleviation of this process have relied on inhibition of VEGF-A activity. Although effective in preventing vascular leak and edema, this approach also leads to the loss of normal vasculature and multiple related side effects. We have developed an alternative strategy that uses anti-syndecan-2 polyclonal antibody (anti-Sdc2 pAb) to block VEGF-A-induced permeability without interfering with other VEGF-A activities. The effect of anti-Sdc2 pAb therapy was assessed in vitro using a transendothelial electrical resistance (TEER) assay, as well as staining of the endothelial cell junction, and in vivo in the laser-induced choroidal neovascularization (CNV) model. Anti-Sdc2 pAb blocked VEGF-A-induced permeability in vitro, and both local intravitreal injections and systemic intravenous treatments with anti-Sdc2 pAb were as effective as intravitreal anti-VEGF therapy in reducing edema, size of retinal lesions, and local inflammation in this model. Post-injury neovascularization was not affected by treatment with anti-Sdc2 pAb. These findings indicate that anti-Sdc2 pAb therapy can be an effective alternative to anti-VEGF-A approaches for suppression of edema and to prevent retinal lesions in wet neovascular AMD (nAMD). Intravitreal anti-Sdc2 treatment may avoid side effects observed with the long-term anti-VEGF therapy, and systemic treatment with an anti-Sdc2 pAb antibody can address the issues associated with repeated intravitreal injections.

Uveal metastasis: clinical characteristics, treatment, and prognostic factors in a cohort of 161 patients in China.

To investigate the clinical and prognostic features of uveal metastasis in a Chinese population and compare these features across different primary cancers. Retrospective cross-sectional study. 161 patients with uveal metastasis at Beijing Tongren Hospital. Clinical characteristics of the primary tumour and uveal metastasis, treatments and outcomes were reviewed. Tumor regression was assessed using B-scan ultrasonography to measure changes in tumor height. Among 161 patients, 185 eyes had uveal metastasis. Lung cancer was the most common primary tumour (49.4%), followed by breast cancer (22.4%), kidney cancer (4.3%). Uveal metastasis was the initial cancer manifestation in 39 patients (24.2%). Unilateral involvement was predominant (86.3%), with the choroid being the most common site (91%). Compared with lung cancer and other cancers, breast carcinoma patients developed uveal metastasis at a younger age (p < 0.001), had a longer interval to uveal metastasis diagnosis (0.67, 4.19, and 6.27 years, p < 0.0001), were prone to be bilateral (11.1%, 9.1%, and 27.8%; p < 0.05) and exhibited lower tumour height (4.47 ± 2.49 mm and 4.88 ± 3.01 mm, 3.09 ± 2.46 mm; p < 0.01). Local treatments (133 eyes) included plaque radiotherapy (PRT, brachytherapy), transpupillary thermotherapy (TTT), anti-VEGF and enucleation. The tumour regression correlated with increased tumor height (r = 0.5699; p < 0.05) in eyes treated with PRT (n = 15). Despite effective local tumour control, the 1-year, 3-year, and 5-year survival rates were 72.61%, 31.82%, and 19.84%, respectively (n = 103). Among the 54 deceased patients, 27 (50%) died within one year following the diagnosis of uveal metastasis. The mean survival was 18.84 months. Extraocular metastasis correlated with shorter survival (p < 0.05). This study provides a comprehensive analysis of uveal metastasis in Chinese patients, highlighting the distinct characteristics from various primaries. Although survival rates remain uncertain, local therapies were effective at achieving ocular tumor control, which aligns with the expectations for patients battling metastatic cancers.

Azithromycin-loaded PLGA microspheres coated with silk fibroin ameliorate inflammation and promote periodontal tissue regeneration.

Periodontitis, a widespread inflammatory disease, is the major cause of tooth loss in adults. While mechanical periodontal therapy benefits the periodontal disease treatment, adjunctive periodontal therapy is also necessary. Topically applied anti-inflammatory agents have gained considerable attention in periodontitis therapy. Although azithromycin (AZM) possesses excellent anti-inflammatory properties, its bioavailability is limited owing to poor water solubility and the absence of sustained release mechanisms. Herein, we synthesized biodegradable microspheres (AZM@PLGA-SF) for sustained AZM release to locally ameliorate periodontal inflammation and facilitate periodontal tissue regeneration. AZM was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres (AZM@PLGA) using single emulsion-solvent evaporation, followed by surface coating with silk fibroin (SF) via electrostatic adsorption, reducing the initial burst release of AZM. In vivo, local treatment with AZM@PLGA-SF microspheres significantly reduced periodontal inflammation and restored periodontal tissue to healthy levels. Mechanically, the formulated microspheres regulated the periodontal inflammatory microenvironment by reducing the levels of pro-inflammatory cytokines (tumor necrosis factor -α, interleukin [IL]-6, interferon-γ, IL-2, and IL-17A) in gingival crevicular fluid and promoted the expression of anti-inflammatory cytokines (IL-4 and IL-10). AZM@PLGA-SF microspheres demonstrated excellent biological safety. Therefore, we introduce an anti-inflammatory therapy for periodontitis with substantial potential for mitigating periodontal inflammation and encouraging the repair and regeneration of periodontal tissues.

Biomaterials enhancing localized cancer therapy activated anti-tumor immunity: a review.

Localized cancer therapies such as radiotherapy, phototherapy, and chemotherapy are precise cancer treatment strategies aimed at minimizing systemic side effects. However, cancer metastasis remains the primary cause of mortality among cancer patients in clinical settings, and localized cancer treatments have limited efficacy against metastatic cancer. Therefore, researchers are exploring strategies that combine localized therapy with immunotherapy to activate robust anti-tumor immune responses, thereby eradicating metastatic cancer. Biomaterials, as novel materials, exhibit great potential in biomedical applications and have achieved great progress in clinic translation. This review introduces biomaterials and their applications in research focused on enhancing localized cancer treatment activated anti-tumor immunity. Additionally, the current challenges and future directions of biomaterials are also discussed, providing insights and references for related research.

Impact of immune checkpoint inhibitors and local radical treatment on survival outcomes in synchronous oligometastatic NSCLC

Impact of immune checkpoint inhibitors and local radical treatment on survival outcomes in synchronous oligometastatic NSCLC

Designing iron oxide & silver nanocomposites with phyto- and fungo chemicals for biomedicine: lessons learned.

Multifunctional nanoparticles for biomedical applications are widely researched and constantly developed because they provide wider possibilities for therapy and diagnostics. This work aims to summarise our findings towards the design of multifunctional complex iron oxide and silver nanoparticles (NPs) produced from the plants Zingiber officinale and Hypericum perforatum and mushrooms Amanita muscaria and Sparassis crispa. It was revealed that the antimicrobial and anticancer properties of the NPs were a consequence of the combination of silver and phyto- and fungo-chemicals originating from natural species. Moreover, the photoactive properties of the complex iron oxide and silver nanoparticles promoted photodynamic therapy (λexc = 405 nm) that significantly improved the antibacterial (E. coli, S. aureus, B. pumilus, P. fluorescence) and anticancer (HeLa, U2OS cells) effects. Notably, the gel formulations of the NPs based on hyaluronic and alginic acids had advantages over the aqueous dispersions of the NPs. For instance, being embedded into a hyaluronic acid gel, the NPs were more effective against cancer cells due to the improved uptake of hyaluronic acid by cancer cells. Another advantage of gel formulations of the NPs was connected with their microstructural properties; the nanocomposite gel adjusted its microstructure to the substrate topology, mimicking the substrate scale and pattern. Thus, complex ultrasmall iron oxide and silver nanoparticle NPs synthesized with natural extracts and their gel formulations may find diverse applications in the biomedical field, particularly for local cancer treatment and as post-operative bone or tissue scaffold after cancer or chronic osteomyelitis surgery.

Long-term outcome for neoadjuvant versus adjuvant chemotherapy in early breast cancer and the prognostic impact of nodal therapy response: A population-based study.

Although neoadjuvant systemic treatment for non-metastatic breast cancer has gained ground during the past decade, there is no compelling evidence that it improves overall survival compared to primary tumor resection and adjuvant treatment. At the same time, the approach to responders to neoadjuvant treatment in the axilla is evolving. This is a retrospective analysis of a prospectively collected population-based registry. Patients that received neoadjuvant (n=2126) or adjuvant chemotherapy (n=4754) for non-metastatic breast cancer during 2007-2020 in the Stockholm-Gotland region, which comprises 25% of the entire Swedish population, were included. Overall survival of patients treated preoperatively and postoperatively was compared using inverse probability treatment weighting and landmark analysis. The prognostic impact of change between prechemotherapy clinical to postchemotherapy pathologic nodal stage (cN/pN) in women receiving neoadjuvant treatment was investigated. Median follow-up was 4.93 years. There was no difference in adjusted overall survival between adjuvant (reference) and neoadjuvant treatment in the entire population (HR=1.38, 95% CI 0.98-1.93, p=0.062) or in breast cancer subtypes. Patients converting from positive clinical to negative pathologic nodal stage (cN+/pN0) had improved outcomes compared to cN0/pN0 or patients with pN0 following primary surgery. These patients had a particular disease trajectory, with early peak in risk of death followed by quick and sustained decrease. There was no difference in survival of patients treated with neoadjuvant versus adjuvant systemic therapy for non-metastatic breast cancer. Patients with cN+/pN0 have excellent prognosis and represent potential candidates for de-escalation of local and systemic treatment.

Neoadjuvant chemoradiotherapy in locally advanced and locally recurrent colon cancer

BackgroundWhile systemic management of high risk colon cancer is well addressed, advances in local management remain incremental. This study aims to identify a group of colon cancer patients where local management remains a challenge, and where intensifying local treatment with radiotherapy is potentially beneficial to minimise the risk of an R1 resection. MethodsPatients with select cT4 locally advanced primary colon (LAPC) (n=40) and locally recurrent colon (LRC) (n=48) adenocarcinomas who received neoadjuvant radiotherapy from 2005 to 2020 were studied. Radiotherapy prescription was 45-50.4 Gy in conventional fractionation. Estimated median follow-up time was 8.1 years and 6.3 years for the LAPC and LRC groups, respectively. ResultsThe most common primary site was the sigmoid colon (n=61). In the LAPC group, surgery was performed in 90% (n=36), 81% (n=29) of which were R0 resections, with pathologic downstaging occurring in 66.7% (n=24). In the LRC group, surgery was possible in 79.2% (n=38), 65.8% (n=25) of which were R0 resections. For the LAPC group, 13% (n=5) had local failures (hazard rate 3%, 95%CI 1-6%), 38% (n=14) had any disease progression (hazard rate 9%; 95%CI 5-14), and 55% (n=22) were alive at the end of the follow-up period (hazard rate 8%; 95%CI 5-13). For the LRC group, 35% (n=17) had local failures (5-year LFFS: 53%; 95%CI: 37-74), and 61% (n=30) had any disease progression (5-year PFS: 28%; 95%CI: 17% - 48%). 5-year OS for the LRC group was 50% (95%CI: 37-68). There was no 30-day mortality. ConclusionLocal management of high risk colon cancer remains a challenge. Future studies in neoadjuvant chemoradiation and systemic therapy, and staging methodology in identifying the high risk group are urgently needed.