Rassegna della letteratura – aprile 2019

Trattamento loco-regionale

(chirurgia oncologica, chirurgia  plastica-ricostruttiva, radioterapia)

Yao Y, Sun L et Al. – Breast-Conserving Surgery in Patients With Mammary Paget’s Disease.- J Surg Res. 2019 Apr 23;241:178-187. doi: 10.1016/j.jss.2019.03.025.

Background: We aimed to analyze the association between Paget’s disease (PD) and breast cancer (BC) subtypes and compare the effect of breast-conserving surgery (BCS) as a local treatment with mastectomy for PD.

Methods: Data of patients with histologic type International Classification of Diseases-0-3 8540-8543 who were treated from 1973 to 2014 were retrieved from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. A chi-square test was used to identify differences in categorical data among different groups. Overall survival (OS) was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, sequential landmark analysis, and propensity score-matched analysis.

Results: The study cohort included 5398 patients. Triple-negative BC accounted for the fewest patients with PD-only (1/22, 4.54%), Paget’s disease-ductal carcinoma in situ (PD-DCIS) (3/48, 6.25%), and Paget’s disease-invading ductal carcinoma (PD-IDC) (23/352, 6.53%). According to the results of the log-rank test and Cox analysis, the 10-year OS rates were similar for the BCS and mastectomy subgroups among patients with PD-DCIS or PD-IDC. Furthermore, there were no significant differences in survival benefits among the different surgeries after propensity score matching. Landmark analyses for OS of patients with PD-DCIS or PD-IDC surviving more than 1, 3, and 5 y showed no significant differences in survival. There were statistical differences in 10-year OS rates for patients with PD-DCIS or PD-IDC who underwent radiation therapy, or not, following BCS (both, P < 0.001).

Conclusions: For patients with PD-DCIS or PD-IDC, breast conservation therapy with lumpectomy and radiation is an effective local treatment strategy, compared with mastectomy.

De Rose F, Fogliata A et Al. – Postmastectomy radiation therapy using VMAT technique for breast cancer patients with expander reconstruction. – Med Oncol. 2019 Apr 25;36(6):48. doi: 10.1007/s12032-019-1275-z.

Background: Postmastectomy radiotherapy (PMRT) following immediate breast reconstruction is increasingly adopted in the management of breast cancer patients. We retrospectively evaluate the complication rates of PMRT using VMAT technique to immediate tissue expander-based reconstructions and the possible impact of tissue expander volume on radiotherapy planning. We reviewed the data of patients who underwent immediate expander breast reconstruction and received PMRT with VMAT (50 Gy in 25 fractions) on the reconstructed breast and axillary levels III-IV. Neoadjuvant or adjuvant systemic therapy was administered in most of the patients. Autologous fat grafting was routinely performed at the time of second-stage reconstruction. Between 2015 and 2017, PMRT was delivered to 46 consecutive patients (median age 50 years) with expander reconstruction. Median follow-up was 27 months (range 10-41). Two patients (4.3%) had a reconstruction failure, as expander rupture and infection, following the first- and the second-stage reconstruction, respectively. In most cases expanders were completely inflated before PMRT (65.2%). Median expander volume before PMRT was 425 cm3 (range 150-700 cm3). The amount of expander inflation did not significantly affect dosimetry, except for skin dose, with a surface receiving more than 30 Gy of 36.6 ± 0.9 cm2 and 47.0 ± 2.5 cm2 for a volume expander below or above the median, respectively. However, this variable was not predictor for complications. Disease progression was recorded in 15.2% of patients. PMRT using VMAT technique for breast cancer patients with expander reconstruction is associated with a very low complication rate. The expander volume before PMRT does not significantly compromise radiotherapy dose distribution.

DeCesaris C, Rice SR et Al.- Quantification of Acute Skin Toxicities in Breast Cancer Patients Undergoing Adjuvant Proton vs. Photon Radiation Therapy: A single institutional experience.Int J Radiat Oncol Biol Phys. 2019 Apr 24. pii: S0360-3016(19)30647-9. doi: 10.1016/j.ijrobp.2019.04.015.

Background: Acute skin toxicity in the form of radiation dermatitis and/or skin hyperpigmentation is a common problem experienced by patients undergoing breast irradiation. Proton radiation has been thought to deliver higher doses to skin compared to photon radiation due to differences in the physical properties between photons and protons, however, limited literature exists directly comparing toxicity outcomes.

Methods: The highest recorded grades of acute radiation dermatitis (RD) and skin hyperpigmentation (SH) were analyzed in 86 patients undergoing adjuvant radiation therapy to the breast with or without regional lymph nodes after lumpectomy (BCS) or mastectomy with either proton pencil-beam scanning (n=39) or photon (n=47) radiotherapy within a single institution to analyze differences in severity of acute skin reactions. For 34/47 photon and 33/39 proton patients, a “skin” contour was retroactively created in our treatment planning systems and multiple dosimetric parameters were calculated to quantify objective radiation doses received by skin.

Results: On Chi-Square analysis, the highest reported grade of radiation dermatitis was significantly higher in women undergoing proton radiation compared to photon radiation; ≥ grade 2 RD was present in 69.2% vs 29.8% of patients receiving proton and photon therapy, respectively (p=0.002). Rates of grade 3 RD were 5.1% vs 4.3% for proton vs photon radiation, respectively (p=.848). Overall, there were no significant differences in rates of SH between modalities. There were no grade 4-5 toxicities in either cohort

Conclusions: When compared to patients receiving photon radiation, a significantly higher rate of ≥ Grade 2 RD was observed in patients undergoing proton radiation, with very low rates of grade 3 toxicity in both groups. Rates of skin hyperpigmentation did not differ significantly between modalities. Women should be counseled regarding the possibility of increased grade 2 toxicities, though this may present a dosimetric advantage for physicians when treating patients in the post-mastectomy setting, or when skin was involved on presentation.

Chang JS, Song SY et Al. – Influence of Radiation Dose to Reconstructed Breast Following Mastectomy on Complication in Breast Cancer Patients Undergoing Two-Stage Prosthetic Breast Reconstruction. – Front Oncol. 2019 Apr 9;9:243. doi: 10.3389/fonc.2019.00243.

Background: This study investigated the association between radiation dose and complication rate in patients who underwent breast reconstruction to understand the role of radiation hypofractionated regimen, boost radiation therapy (RT), and RT techniques.

Methods: We retrospectively evaluated 75 patients treated with post-mastectomy adjuvant RT for breast cancer in the setting of two-stage prosthetic breast reconstruction. Near maximum radiation dose (Dmax) in the 2 or 0.03 cc of reconstructed breast or overlying breast skin was obtained from dose-volume histograms.

Results: Post-RT complications occurred in 22.7% of patients. Receiver operating characteristic analysis showed that all near Dmax parameters were able to predict complication risk, which retained statistical significance after adjusting other variables (odds ratio 1.12 per Gy, 95% confidence interval 1.02-1.23) with positive dose-response relationship. In multiple linear regression model (R 2 = 0.92), conventional fractionation (β = 11.7) and 16 fractions in 2.66 Gy regimen (β = 3.9) were the major determinants of near Dmax compared with 15 fractions in 2.66 Gy regimen, followed by utilization of boost RT (β = 3.2). The effect of bolus and dose inhomogeneity seemed minor (P > 0.05). The location of hot spot was not close to the high density metal area of the expander, but close to the surrounding areas of partially deflated expander bag.

Conclusions: This study is the first to demonstrate a dose-response relationship between risk of complications and near Dmax, where hypofractionated regimen or boost RT can play an important role. Rigorous RT-quality assurance program and modification of dose constraints could be considered as a critically important component for ongoing trials of hypofractionation. Based on our findings, we initiated a multi-center retrospective study (KROG 18-04) and a prospective study  to validate our findings

Wang M, Chen H et Al. – Post-mastectomy immediate breast reconstruction is oncologically safe in well-selected T4 locally advanced breast cancer: a large population-based study and matched case-control analysis. – Breast Cancer Res Treat. 2019 Apr 24. doi: 10.1007/s10549-019-05240-w.

Background: Although it is well accepted that the survival outcome is most probably unaffected by immediate breast reconstruction (IBR) for T1-T3 tumors, the safety of IBR in T4 locally advanced breast cancer (LABC) remains unclear.

Methods: By using data from the Surveillance, Epidemiology, and End Results (SEER) database, the trend of IBR for female T4 LABC patients undergoing mastectomy, chemotherapy and radiotherapy was explored. The predictors of IBR in T4 LABC were evaluated by multivariate logistic regression. The survival outcomes were compared by means of Cox hazards models adjusting for known clinicopathological variables and stratifying on the T stage and contralateral prophylactic mastectomy (CPM).

Results: Altogether 714 cases underwent IBR between 1998 and 2015. The IBR cohort had a lower percentage of cases with T4d disease whereas higher percentage with CPM. The IBR rate was 10.1% and increased from 4.1% in 1998 to 17.7% in 2015. Since 2009, the rate of implant-based IBR exceeded that of the autologous tissue method. An age less than 45 years (OR 2.930, 95% CI 2.299-3.735) and CPM (OR 2.758, 95% CI 2.306-3.299) were the strongest predictors of IBR. In the 1:2 matched case-control analysis, IBR was not an independent prognostic factor for breast cancer specific-survival (BCSS) (HR 0.893, p = 0.236, 95% CI 0.741-1.077) and overall survival (OS) (HR 0.886, p = 0.183, 95% CI 0.741-1.059). BCSS and OS were similar among patients undergoing IBR whether they underwent CPM or not and whether they were inflammatory breast cancer (IBC) or not.

Conclusions: IBR is oncologically safe in well-selected T4 LABC

Stick LB, Vogelius IR et Al. – Inverse radiotherapy planning based on bioeffect modelling for locally advanced left-sided breast cancer. – Radiother Oncol. 2019 Apr 3;136:9-14. doi: 10.1016/j.radonc.2019.03.018.

Background: Treatment planning of radiotherapy (RT) for left-sided breast cancer is a challenging case. Several competing concerns are incorporated at present through protocol-defined dose-volume constraints, e.g. cardiac exposure and target coverage. Such constraints are limited by neglecting patient-specific risk factors (RFs). We propose an alternative RT planning method based solely on bioeffect models to minimize the estimated risks of breast cancer recurrence (BCR) and radiation-induced mortality endpoints considering patient-specific factors.

Methods: Thirty-nine patients with left-sided breast cancer treated with comprehensive post-lumpectomy loco-regional conformal RT were included. An in-house particle swarm optimization (PSO) engine was used to choose fields from a large set of predefined fields and optimize monitor units to minimize the total risk of BCR and mortality caused by radiation-induced ischaemic heart disease (IHD), secondary lung cancer (SLC) and secondary breast cancer (SBC). Risk models included patient age, smoking status and cardiac risk and were developed using published multi-institutional data.

Results: For the clinical plans the normal tissue complication probability, i.e. summed risk of IHD, SLC and SBC, was <3.7% and the risk of BCR was <6.1% for all patients. Median total decrease in mortality or recurrence achieved with individualized PSO plans was 0.4% (range, 0.06-2.0%)/0.5% (range, 0.11-2.2%) without/with risk factors.

Conclusions: Inverse RT plan optimization using bioeffect probability models allows individualization according to patient-specific risk factors. The modelled benefit when compared to clinical plans is, however, modest in most patients, demonstrating that current clinical plans are close to optimal. Larger gains may be achievable with morbidity endpoints rather than mortality.

Baghani HR, Robatjazi M et Al. – Breast intraoperative electron radiotherapy: Image-based setup verification and in-vivo dosimetry. – Phys Med. 2019 Apr;60:37-43. doi: 10.1016/j.ejmp.2019.03.017. Epub 2019 Mar 24.

Background: Single fraction nature of intraoperative radiotherapy highly demands a quality assurance procedure to qualify both beam setup and treatment delivery. The aim of this study is to evaluate the treatment setup during breast intraoperative electron radiotherapy (IOERT) and in-vivo dose delivery verification.

Methods: Twenty-five breast cancer patients were enrolled and setup verification for each case was performed using C-arm imaging. The received dose by surface and distal end of target was measured by EBT2 film. The significance level of difference between obtained dosimetry results and predicted ones was evaluated by the T statistical test.

Results: Acquired C-arm images in two different oblique views revealed any misalignment between the applicator and shielding disk. The mean difference between the measured surface dose and expected one was 1.8% ± 1.2 (p = 0.983) while a great disagreement, 11.1% ± 1.5 (p < 0.001), was observed between the measured distal end dose and expected one. This discrepancy is mainly correlated to the backscattering effect from the shielding disk. Target depth nonuniformities can also contribute to this remarkable difference.

Conclusions: Employing the intraoperative imaging for IOERT setup verification can considerably improve the treatment quality. Therefore, it is suggested to implement this imaging procedure as a part of treatment quality assurance. Favorable agreement between the predicted and measured surface doses demonstrates the applicability of EBT2 film for dose delivery verification. The results of in-vivo dosimetry showed that the electron backscattering from employed shielding disk can affect the received dose by the distal end of tumor bed

Behluli I, Le Renard P et Al. – Oncoplastic breast surgery versus conventional breast-conserving surgery: a comparative retrospective study. – ANZ J Surg. 2019 Apr 16. doi: 10.1111/ans.15245.

Background: In addition to conventional breast-conserving surgery (BCS), oncoplastic breast surgery (OBS) is an operation technique that strives simultaneously to increase oncological safety and patient’s satisfaction. It is the combination of the best-proven techniques in plastic surgery with surgery for breast cancer. In a growing number of indications, OBS overcomes the limit of conventional BCS by allowing larger resection volumes while avoiding deformities. The aim of our retrospective study (2012-2014) was to compare oncological outcomes of OBS versus BCS.

Methods: We compared two groups of patients with primary non-metastatic breast tumours: group A (n = 291), where BCS was performed, versus group B (n = 52), where OBS was performed. Surgical interventions were performed in German and Swiss teaching hospital settings. The surgeon for group B had subspecialist training in OBS. We assessed outcome in term of re-excision rates, resection margin and complications.

Results: Groups were homogenous (no significant differences in terms of age, tumour size, tumour type or grade). The resection margin was larger in group B (7 mm) than in group A (3 mm). Re-excision rate of group B (8%) was significantly lower than in group A (31%). Complication rates were comparably low in groups A and B.

Conclusions: Despite the limits of retrospective design, our study confirms that OBS is safe and reduces the re-excision rates and the need for further surgery. OBS has the potential to improve oncological care and should be more widely adopted.