Surgical techniques for breast cancer have been refined over the past decades to deliver an aesthetic outcome as close as possible to the contralateral intact breast. Current surgery further allows ...excellent aesthetic outcome even in case of mastectomy, by performing skin sparing or nipple sparing mastectomy in combination with breast reconstruction. In this review we discuss how to optimise post-operative radiation therapy after oncoplastic and breast reconstructive procedures, including dose, fractionation, volumes, surgical margins, and boost application.
•New surgical procedures for breast cancer poses new challenges for the radiation oncologists.•Oncoplastic breast surgery may question the ability to apply a tumour bed boost.•Skin sparing/nipple sparing mastectomies should be planned to assure clear superficial margins.•Radiation therapy should be adapted per case to provide maximal clinical benefit and reduce toxicity.•Multidisciplinary teamwork is needed to plan the most appropriate locoregional therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Electroporation of cells with short, high-voltage pulses causes a transient permeabilization of cell membranes that permits passage of otherwise nonpermeating ions and molecules. In this study, we ...illustrate how electroporation with isotonic calcium can achieve highly effective cancer cell kill in vivo. Calcium electroporation elicited dramatic antitumor responses in which 89% of treated tumors were eliminated. Histologic analyses indicated complete tumor necrosis. Mechanistically, calcium electroporation caused acute ATP depletion likely due to a combination of increased cellular use of ATP, decreased production of ATP due to effects on the mitochondria, as well as loss of ATP through the permeabilized cell membrane. Taken together, our findings offer a preclinical proof of concept for the use of electroporation to load cancer cells with calcium as an efficient anticancer treatment. Electroporation equipment is already used clinically to enhance the delivery of chemotherapy to superficial tumors, with trials on internal tumors in progress, enabling the introduction of calcium electroporation to clinical use. Moreover, the safety profile, availability, and low cost of calcium facilitate access to this technology for many cancer patients in developed and developing countries.
Calcium electroporation may offer a simple general tool for anticancer therapy. Transient permeabilization of cancer cell membranes created by applying short, high-voltage pulses in tumors enables ...high calcium influxes that trigger cell death. In this study, we compared the relative sensitivity of different human tumor models and normal tissues to calcium electroporation. Plasma membrane Ca
-ATPase (PMCA) protein expression was confirmed
in all cancer cell lines and normal primary dermal fibroblasts studied. In all tumor types tested
, calcium electroporation effectively induced necrosis, with a range of sensitivities observed (36%-88%) 2 days after treatment. Necrosis was induced using calcium concentrations of 100-500 mmol/L and injection volumes 20%-80% of tumor volume. Notably, only limited effects were seen in normal tissue. Calcium content increased >7-fold in tumor and skin tissue after calcium electroporation but decreased in skin tissue 4 hours after treatment to levels comparable with untreated controls, whereas calcium content endured at high levels in tumor tissue. Mechanistic experiments
indicated that calcium influx was similar in fibroblasts and cancer cells. However, we observed decreased PMCA expression in cancer cells compared with fibroblasts, offering a potential explanation for the different calcium content in tumor cells versus normal tissues. Overall, our results suggest that calcium electroporation can elicit a rapid and selective necrosis of solid tumors, with limited deleterious effects on surrounding normal tissues.
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Abstract Background HPV/p16-positive head and neck cancers (HNSCC) show superior response to radiotherapy, compared with virus-negative tumours. Tumour hypoxia induces radioresistance and the ...randomised DAHANCA 5 trial found that the hypoxic cell radiosensitiser nimorazole significantly improved the outcome in HNSCC. Using p16-status as a retrospective stratification parameter, we aimed to assess the influence of p16-expression on the response to nimorazole in HNSCC. Materials and methods Pre-treatment tumour blocks were available from 331 of the 414 patients in the DAHANCA 5 trial and evaluated by immunohistochemistry for p16-expression. The influence of p16-expression on outcome was analysed as a function of treatment group (nimorazole/placebo) 5 years after radiotherapy. Results Overall, patients treated with nimorazole had significantly better loco-regional control than did those given placebo: hazard ratio (HR) 0.70 95% CI 0.52–0.93. Positive expression of p16 also significantly improved outcome after radiotherapy (0.41 0.28–0.61). In the subgroup of patients with p16-negative tumours, loco-regional failure was more frequent in the placebo group than in the nimorazole group (0.69 0.50–0.95). However, in the p16-positive group, patients treated with nimorazole had a loco-regional control rate similar to patients given placebo (0.93 0.45–1.91). Conclusions HPV/p16-expression significantly improved outcome after radiotherapy in HNSCC. Hypoxic modification improved outcome in HPV/p16-negative tumours but was of no significant benefit in HPV/p16-positive tumours, suggesting that hypoxic radioresistance may not be clinically relevant in these tumours.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Breast cancer is the most common malignancy, and the majority of the patients are diagnosed at an early disease stage. Breast conservation is the preferred locoregional approach, and oncoplastic ...breast conservation surgery is becoming more popular. This narrative review aims to discuss the challenges and uncertainties in target volume definition for postoperative radiation after these procedures, to improve radiation therapy decisions and encourage multidisciplinary.
•Postoperative radiation therapy is an integral part of breast conserving therapy.•The tumour bed is the most important target volume after breast conservation including oncoplastic procedures.•Tumour bed identification after oncoplastic procedure is at times impossible to identify or define.•The orientation of positive margins after oncoplastic procedures at times impossible to identify or define.•Proper pre-operative planning, by a multidisciplinary team that understands each modality treatment is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Involved resection margins after breast conserving surgery (BCS) often require a re-operation with increased patient anxiety and risk of impaired cosmesis.
We investigated the number of re-operations ...due to involved resection margins after BCS comparing digital breast tomosynthesis(DBT) with X-ray for intraoperative margin evaluation.
Furthermore, we assessed the diagnostic accuracy of these methods to predict histopathological margin status. Finally, we evaluated risk factors for re-operation.
In this randomized, non-blinded study, 250 invasive breast cancer patients were randomized (1:1), whereof 241 were analyzed intraoperatively with either DBT (intervention, n = 119) or X-ray (standard, n = 122). Pearson's chi-squared test, Fisher's exact test, t-test, logistic and ordinal regression analysis was used as appropriate.
No difference was found in the number of re-operations between the DBT and X-ray group (16.8 % vs 19.7 %, p = 0.57), or in diagnostic accuracy to predict histopathological margin status (77.5 %, CI: 68.6–84.9 %) and (67.3 %, CI: 57.7–75.9 %), respectively. We evaluated 5 potential risk factors for re-operation: Ductal carcinoma in situ (DCIS) outside tumor, OR = 9.4 (CI: 4.3–20.6, p < 0.001); high mammographic breast density, OR = 6.1 (CI: 1.0–38.1, p = 0.047); non-evaluable margins on imaging, OR = 3.8 (CI: 1.3–10.8, p = 0.016); neoadjuvant chemotherapy, OR = 3.0 (CI: 1.0–8.8, p = 0.048); and T2 tumor-size, OR = 2.6 (CI: 1.0–6.4, p = 0.045).
No difference was found in the number of re-operations or in diagnostic accuracy to predict histopathological margin status between DBT and X-ray groups. DCIS outside the tumor showed the highest risk of re-operation. Intraoperative methods with improved visualization of DCIS are needed to obtain tumor free margins in BCS.
•No difference in re-operations between using digital breast tomosynthesis and specimen X-ray in breast conserving surgery.•Ductal Carcinoma in Situ (DCIS) in the resected margins was strongly associated with re-operation.•Improved imaging of DCIS during breast conserving surgery is needed to obtain tumor free margins.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The current review paper was written in collaboration with breast cancer surgeons from the European Breast Cancer Research Association of Surgical Trialists (EUBREAST), a breast pathologist from the ...Danish Breast Cancer Group (DBCG), and representatives from the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer course. Herein we summarize the different mastectomies and reconstruction procedures and define high-risk anatomical areas for breast cancer recurrences, to further specify the challenges in the surgical procedure, histopathological evaluation, and target volumes in case of postmastectomy irradiation, as recommended by the ESTRO guidelines according to the surgical procedure. The paper has original figures and illustrations for all disciplines for in-depth understanding of the differences between the procedures.
•Mastectomy techniques and reconstruction evolved to improve cosmetic outcomes.•Different techniques maybe associated with different amount of residual breast tissue.•More data is needed to estimate who are the patients at risk for residual disease or recurrence.•Multidisciplinary work needed to individualise treatment for optimal oncological outcomes while maintaining the significant improvements in achieving better cosmesis for these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this narrative review, we aim to explore the ability of radiation therapy to eradicate breast cancer regional node metastasis. It is a journey through data of older trials without systemic therapy ...showing the magnitude of axillary therapy (surgery versus radiation) on cancer control. Considering that both systemic and loco-regional therapies were shown to reduce any recurrence with a complex interaction, our review includes surgical, radiation, and radiobiology consideration for breast cancer, and provide our view of future practise. The aim is to provide information optimise radiation therapy in the era of primary systemic therapy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Radiation therapy (RT) has long been fundamental for the curative treatment of breast cancer. While substantial progress has been made in the anatomical and technological precision of RT delivery, ...and some approaches to de-escalate or omit RT based on clinicopathologic features have been successful, there remain substantial opportunities to refine individualised RT based on tumour biology.
A major area of clinical and research interest is to ascertain the individualised risk of loco-regional recurrence to direct treatment decisions regarding escalation and de-escalation of RT. Patient-tailored treatment with RT is considerably lagging behind compared with the massive progress made in the field of personalised medicine that currently mainly applies to decisions on the use of systemic therapy or targeted agents.
Herein we review select literature surrounding the use of tumour genomic biomarkers and biomarkers of the immune system, including tumour infiltrating lymphocytes (TILs), within the management of breast cancer, specifically as they relate to progress in moving toward analytically validated and clinically tested biomarkers utilized in RT.
•The genomic-adjusted radiation dose (GARD) is a non-breast cancer specific, tumour genomic biomarker introduced to personalise the radiation prescription dose. GARD is predictive of benefit from RT.•Currently no prospectively validated association between TILs and response to RT is demonstrated.•Prospective biomarker-driven randomised RT trial data utilizing genomic biomarkers are currently lacking, it is currently too early for biomarker-guided RT in the clinic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several ...aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquaglyceroporins also facilitate the transport of glycerol and are thus involved in cellular metabolism. Transcriptomic analysis revealed that the three aquaglyceroporins, AQP3, AQP7 and AQP9, but not AQP10, are overexpressed in human breast cancer. It is, however, unknown if they are all expressed in the same cells or have a heterogeneous expression pattern. To investigate this, we employed immunohistochemical analysis of serial sections from human invasive ductal and lobular breast cancers. We found that AQP3, AQP7 and AQP9 are homogeneously expressed in almost all cells in both premalignant in situ lesions and invasive lesions. Thus, potential intervention strategies targeting cellular metabolism via the aquaglyceroporins should consider all three expressed aquaglyceroporins, namely AQP3, AQP7 and AQP9.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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