Are We Losing the Final Fight against Cancer?

Despite our increasing understanding of the biology and evolution of the cancer process, it is indisputable that the natural process of cancer creation has become increasingly difficult to cure, as more mutations are found with age. It is significantly more difficult to challenge the curative method when there is heterogeneity within the tumor, as it hampers clinical and genetic categorization. With advances in diagnostic technologies and screening leading to progressive tumor shrinkage, it becomes more difficult over time to evaluate the effects of treatment on overall survival.

Lung-heart toxicity in a randomized clinical trial of hypofractionated image guided radiation therapy for breast cancer.

Background: TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT).

Methods: In a single center 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a composite four-items measure of the time to 10% alteration in any of patient-reported outcomes, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat.

Correction: Storme, G.A. Breast Cancer: Impact of New Treatments? 2023, , 2205.

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Breast Cancer: Impact of New Treatments?

Background: Breast cancer treatment has seen tremendous progress since the early 1980s, with the first findings of new chemotherapy and hormone therapies. Screening started in the same period.

Methods: A review of population data (SEER and the literature) shows an increase in recurrence-free survival until 2000 and it stagnates afterwards.

Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients.

We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort.

Total marrow irradiation reduces organ damage and enhances tissue repair with the potential to increase the targeted dose of bone marrow in both young and old mice.

Total body irradiation (TBI) is a commonly used conditioning regimen for hematopoietic stem cell transplant (HCT), but dose heterogeneity and long-term organ toxicity pose significant challenges. Total marrow irradiation (TMI), an evolving radiation conditioning regimen for HCT can overcome the limitations of TBI by delivering the prescribed dose targeted to the bone marrow (BM) while sparing organs at risk. Recently, our group demonstrated that TMI up to 20 Gy in relapsed/refractory AML patients was feasible and efficacious, significantly improving 2-year overall survival compared to the standard treatment.

Lung Restriction in Patients With Breast Cancer After Hypofractionated and Conventional Radiation Therapy: A 10-Year Follow-up.

Purpose: Previous studies in patients with breast cancer have shown acute radiation therapy-induced reductions of pulmonary diffusing capacity, essentially owing to lung volume restriction. We aimed to assess the long-term effect of 2 radiation therapy regimens, which differed in terms of radiation technique and dose fractionation, on lung function.

Methods And Materials: From a randomized controlled trial comparing conventional 3-dimensional conformal radiation therapy (CR) and hypofractionated tomotherapy (TT), 84 patients with breast cancer (age at inclusion 54 ± 10 [standard deviation] years) could be assessed at baseline, after 3 months, and after 1, 2, 3, and 10 years.

Longitudinal Preclinical Imaging Characterizes Extracellular Drug Accumulation After Radiation Therapy in the Healthy and Leukemic Bone Marrow Vascular Microenvironment.

Purpose: Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia.

First Multimodal, Three-Dimensional, Image-Guided Total Marrow Irradiation Model for Preclinical Bone Marrow Transplantation Studies.

Purpose: Total marrow irradiation (TMI) has significantly advanced radiation conditioning for hematopoietic cell transplantation in hematologic malignancies by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. However, the relapse rate remains high, and the lack of a preclinical TMI model has hindered scientific advancements. To accelerate TMI translation to the clinic, we developed a TMI delivery system in preclinical models.

Breast cancer preoperative FDG-PET, overall survival prognostic separation compared with the lymph node ratio.

Purpose: To evaluate the overall survival prognostic value of preoperative F-fluorodeoxyglucose positron emission tomography (PET) in breast cancer, as compared with the lymph node ratio (LNR).

Methods: Data were abstracted at a median follow-up 14.7 years from a retrospective cohort of 104 patients who underwent PET imaging before curative surgery.

Two-Level Factorial Pre-TomoBreast Pilot Study of Tomotherapy and Conventional Radiotherapy in Breast Cancer: Post Hoc Utility of a Mean Absolute Dose Deviation Penalty Score.

Background: A 2-level factorial pilot study was conducted in 2007 just before starting a randomized clinical trial comparing tomotherapy and conventional radiotherapy (CR) to reduce cardiac and pulmonary adverse effects in breast cancer, considering tumor laterality (left/right), target volume (with/without nodal irradiation), surgery (tumorectomy/mastectomy), and patient position (prone/supine). The study was revisited using a penalty score based on the recently developed mean absolute dose deviation (MADD).

Methods: Eight patients with a unique combination of laterality, nodal coverage, and surgery underwent dual tomotherapy and CR treatment planning in both prone and supine positions, providing 32 distinct combinations.

Axillary Lymph Node Involvement in Breast Cancer: A Random Walk Model of Tumor Burden.

We reinvestigate the relationship between axillary lymph node involvement in breast cancer and the overall risk of death. Patients were women from the Surveillance, Epidemiology, and End Results (SEER) program, aged between 50 and 65 years, presenting a first primary T1-T2 (tumor size ≤5 cm), node-positive, non-metastasized unilateral breast carcinoma, diagnosed from 1988 to 1997, treated with mastectomy without radiotherapy. Hazard ratios (HRs) were computed at each percentage of involved nodes using the proportional hazards model, adjusting for the patient's demographic and tumor characteristics.

Multi-institutional evaluation of MVCT guided patient registration and dosimetric precision in total marrow irradiation: A global health initiative by the international consortium of total marrow irradiation.

Purpose: Total marrow irradiation (TMI) is a highly conformal treatment of the human skeleton structure requiring a high degree of precision and accuracy for treatment delivery. Although many centers worldwide initiated clinical studies using TMI, currently there is no standard for pretreatment patient setup. To this end, the accuracy of different patient setups was measured using pretreatment imaging.

Early assessment of dosimetric and biological differences of total marrow irradiation versus total body irradiation in rodents.

Purpose: To develop a murine total marrow irradiation (TMI) model in comparison with the total body irradiation (TBI) model.

Materials And Methods: Myeloablative TMI and TBI were administered in mice using a custom jig, and the dosimetric differences between TBI and TMI were evaluated. The early effects of TBI/TMI on bone marrow (BM) and organs were evaluated using histology, FDG-PET, and cytokine production.

Combination therapeutics of Nilotinib and radiation in acute lymphoblastic leukemia as an effective method against drug-resistance.

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI) therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR) in combination with TKI therapy overcome chemo-resistance.

Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species.

Auranofin (AF) is an anti-arthritic drug considered for combined chemotherapy due to its ability to impair the redox homeostasis in tumor cells. In this study, we asked whether AF may in addition radiosensitize tumor cells by targeting thioredoxin reductase (TrxR), a critical enzyme in the antioxidant defense system operating through the reductive protein thioredoxin. Our principal findings in murine 4T1 and EMT6 tumor cells are that AF at 3-10 μM is a potent radiosensitizer in vitro, and that at least two mechanisms are involved in TrxR-mediated radiosensitization.

The cost of cancer care is not related to its outcomes.

Solid tumours make up 90% of all proliferative diseases and the main action for cure remains surgery, removing the visible tumour as well as the surrounding tissue. Radiotherapy is an added value for eliminating local microscopic as well as regional disease. Systemic treatment has a small impact on the outcome but has a cost, which is as much as all the other actions such as diagnostic tools and treatments.

Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography.

Purpose: To develop an imaging method to characterize and map marrow composition in the entire skeletal system, and to simulate differential targeted marrow irradiation based on marrow composition.

Methods And Materials: Whole-body dual energy computed tomography (DECT) images of cadavers and leukemia patients were acquired, segmented to separate bone marrow components, namely, bone, red marrow (RM), and yellow marrow (YM). DECT-derived marrow fat fraction was validated using histology of lumbar vertebrae obtained from cadavers.

Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up.

Purpose: To assess the effect of radiation therapy on lung function over the course of 3 years.

Methods And Materials: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years.

Motion management during SBRT for oligometastatic cancer: Results of a prospective phase II trial.

Purpose: To optimize the local control of stereotactic body radiotherapy (SBRT) using the Vero-SBRT system and respiratory motion management in patients with oligometastatic cancer.

Materials And Methods: Patients with five or less metastases were eligible. In metastases with significant motion, a fiducial was implanted for Vero dynamic tracking.

Myeloid-derived suppressor cells reveal radioprotective properties through arginase-induced l-arginine depletion.

Background And Purpose: High arginase-1 (Arg) expression by myeloid-derived suppressor cells (MDSC) is known to inhibit antitumor T-cell responses through depletion of l-arginine. We have previously shown that nitric oxide (NO), an immune mediator produced from l-arginine, is a potent radiosensitizer of hypoxic tumor cells. This study therefore examines whether Arg(+) overexpressing MDSC may confer radioresistance through depleting the substrate for NO synthesis.