Impact of adjuvant radiotherapy on biological and clinical parameters in right-sided breast cancer

PurposeIn patients with right-sided breast cancer (BC) the liver might be partially irradiated during adjuvant radiotherapy (RT). Thus, we performed a prospective observational study to evaluate the dose delivered to the liver, and its potential biological impact.Patients and methodsWe enrolled 34 patients with right-sided BC treated with adjuvant RT. The RT schedules were either the Canadian (42.5 Gy in 16 fx) or standard fractionated (50 Gy in 25 fx) regimen respectively with 9 (26.5%) and 25 (73.5%) patients each, ± a boost of 10–16 Gy. Each patient had a complete blood count and liver enzymes analysis, before starting and during the last week of treatment.ResultsA significant decrease in white blood cells and thrombocytes counts was observed during RT. We observed a significant correlation between certain hepatic parameters and the volume of the irradiated liver and/or the mean liver dose. A significant correlation between the volume of the right lung and the liver mean dose was found (P = 0.008). In the bivariate analysis, a significant correlation between fatigue and the white blood cell count's evolution was observed (P < 0.025).ConclusionWith the standard RT technique, incidental irradiation of the liver was documented in a large number of patients, and some significant hepatic parameters alterations were observed, without an apparent clinical impact, but this study cannot exclude them. The liver mean dose was correlated with the right lung volume suggesting that deep inspiration breath hold (DIBH) techniques may represent a way to decrease the liver dose. These findings need to be evaluated in further larger studies.     

Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases

PurposeStereotactic radiotherapy (SRT) is the standard treatment for brain metastases of non-small-cell lung cancer (NSCLC) and melanoma, mostly in combination with immunotherapy. The objective was to retrospectively evaluate the influence of the time-lapse between immunotherapy and stereotactic radiotherapy on toxicity.Patients and methodsFrom 2016 to 2019, 59 patients treated with SRT for 103 brain metastases of NSCLC (60%) and melanoma (40%) in combination with concomitant immunotherapy (≤ 30 days) were included. The prescribed dose was 20 Gy/1f or 33 Gy/3f at the isocentre and 14 Gy or 23.1 Gy (70%) respectively at the PTV envelope (PTV = GTV + 2 mm). The mean tumour diameter was 14 mm (4–52 mm). The immunotherapies used were anti-PD1 and anti-PDL1. The 103 metastases were classified into 3 groups according to the time-lapse between instatement of immunotherapy and instatement of SRT for the patient concerned: 7 (7%) in group A (≤ 7 days), 38 (37%) in group B (7 to 14 days) and 58 (56%) in group C (14 to 30 days).ResultsThe mean follow-up was 10.1 months. The median overall survival was 11.5 months for NSCLC and 12.5 months for melanoma. The percentage of local control (LC) at one year was 65.1% (93.6% for NSCLC and 26.5% for melanoma). The time-lapse between immunotherapy and SRT was not a significant predictor of LC (P = 0.86), while the histology was (P < 0.001). The proportion of grade ≥ 3 toxicities was 5.1%, and that of radionecrosis was 9.7% (among these patients, 80% were non-symptomatic): 0%, 13.1% and 8.6% for groups A, B and C respectively. The time-lapse between immunotherapy and SRT was not a significant predictor of toxicity. Only tumour volume was a significant predictive factor (P = 0.03).ConclusionThe time lapse between immunotherapy and SRT does not influence brain toxicity. The tumour volume remains the main factor.     

Adaptive radiation therapy: When,how and what are the benefits that literature provides?

PurposeTo identify from the current literature when is the right time to replan and to assign thresholds for the optimum process of replanning. Nowadays, adaptive radiotherapy (ART) for head and neck cancer plays an exceptional role consisting of an evaluation procedure of the prominent anatomical and dosimetric variations. By performing complex radiotherapy methods, the credibility of the therapeutic result is crucial. Image guided radiotherapy (IGRT) was developed to ensure locoregional control and thus changes that might occur during radiotherapy be dealt with.Materials and methodsAn electronic research of articles published in PubMed/MEDLINE and Science Direct databases from January 2004 to October 2020 was performed. Among a total of 127 studies assessed for eligibility, 85 articles were ultimately retained for the review.ResultsThe most noticeable changes have been reported in the middle fraction of the treatment. Therefore, the suggested optimal time to replan is between the third and the fourth week. Anatomical deviations > 1 cm in the external contour, average weight loss > 10%, violation in the dose coverage of the targets > 5%, and violation in the dose of the peripherals were some of the thresholds that are currently used, and which lead to replanning.ConclusionART may decrease toxicity and improve local-control. Whether it is beneficial or not, depends ultimately on each patient. However, more investigation of the changes should be performed in future prospective studies to obtain more accurate results.     

I125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis

PurposeA meta-analysis aimed to systematically evaluate the safety and efficiency of I¹²⁵ irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT).Materials and methodsThe Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software.ResultsTotally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I¹²⁵ irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I¹²⁵ irradiation stent improved the cumulative stent patency rates in 6 months [OR = 1.65, 95% CI (1.32–2.05), P < 0.001] and 12 months [OR = 2.55, 95% CI (1.90–3.42), P < 0.001] and the survival rates in 6 months [OR = 1.77, 95% CI (1.41–2.22), P < 0.001], 12 months [OR = 3.14, 95% CI (2.24–4.40), P < 0.001] and 24 months [OR = 7.39, 95% CI (3.55–15.41), P < 0.001]. However, there was no difference in the objective response rate of PVTT [OR = 1.13, 95% CI (0.87–1.48), P = 0.365], main portal venous pressure and the occurrence adverse event [OR = 0.88, CI = 0.72–1.08, P = 0.212] between two groups.ConclusionI¹²⁵ irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.     

Image-guided total-body irradiation with a movable electronic portal imaging device for bone marrow transplant conditioning

IntroductionTo prevent radiation pneumonitis following total body irradiation (TBI) clinicians usually use lung shield blocks. The correct position of these shields relative to the patient's lungs is usually verified via mega-voltage imaging and computed radiographic (CR) films. In order to improve this time-consuming procedure, we developed in our department a dedicated, movable, real-time imaging system for image-guided TBI.Material & MethodsThe system consists of an electronic portal imaging device (EPID) mounted on a dedicated support whose motion along a rail can be controlled from the linac console outside the bunker room. Images are acquired online using a stand-alone console. To test the system efficacy we retrospectively analyzed data of lung blocks positioning from two groups of 10 patients imaged with EPID or CR-films, respectively.ResultsThe median number of portal images per fraction was 2 (range 1-5) and 1 (range 1-2) for the EPID and the CR-film system, respectively. The minimum time required for an EPID image acquisition, without interpretation and no need of patient position correction in the bunker, was 20 seconds against 214 seconds for the CR-film. Lung shielding positioning in the right-left and superior-inferior directions was improved using the EPID system (p< 0.01).ConclusionsCompared to CR-films, our movable real-time imaging EPID system is a simple technical solution able to reduce the minimum imaging time for lung shielding by a factor of 10. With the increased possibility to acquire more images as compared to CR-film system the EPID system has the potential to improve patient alignment, as well as patient's comfort and overall setup time.     

Optic nerve motion and gaze direction: Their impact on intraorbital tumor radiotherapy

PurposeManagement of inter- and intra-fraction movements of target volumes and organs at risk (OARs) during radiotherapy is essential. While there is little OAR or target volume movement, the movements and orientation of the eyes can be significant during radiotherapy and they can affect the position of the optic nerve. The objective of the present study was to assess the variations of the optic nerve position due to gaze direction and to discuss their clinical consequences on the radiation treatment of intraorbital tumors.Material and methodsThree patients without a history of oculomotor nerve palsy underwent six CT acquisitions with a thermoplastic mask: eyes open with different gaze directions (straight ahead, left, right, up, down) and eyes closed. The acquisition with the straight-ahead gaze was chosen as the reference position. Left and right optic nerves were segmented on the six acquisitions, and total volumes and maximum amplitude motions were calculated in three dimensions.ResultsMaximum differences were observed while looking left and up, with a median maximum amplitude of 5 and 6 mm [range: 2–7 mm], respectively. These motions induced a position variation of more than 50% of the volume of the optic nerve (compared to the reference position). Greater variations of motion were observed for the anterior portion of the nerve. The gaze position with the fewest variations compared to the reference position was eyes closed.ConclusionOptic nerve positions vary significantly due to the gaze direction, especially for the anterior portion of the nerve. These variations should be taken into account for the treatment of small intraorbital tumors involving the anterior third of the optic nerve.     

Adult parameningial alveolar rhabdomyosarcoma: Case report and literature review

Alveolar rhabdomyosarcoma (ARMS) represents the most common childhood soft tissue sarcoma, but they are rarely seen among adults. Most of the protocols for adults are adapted from pediatric protocols. Here we report a case of a 53-year-old woman diagnosed with a nasal alveolar rhabdomyosarcoma, stage IV at diagnosis, treated by chemotherapy (a regimen inspired from the pediatric protocole pEpSSG RMS 2005) which led to partial response followed by chemo-radiotherapy. We performed a systematic review of adult head and neck ARMS and found 29 cases. Primary chemotherapy with different protocols (VAC, VAI or VIE) should be done followed by surgery and/or external beam radiotherapy (preferably with IMRT). EBRT seems beneficial to every ARMS with a dose around 50 Gy in a conventional fractionation, eventually completed with a boost on residual tumor. The target volume must be defined on pre-chemotherapy imaging. Brachytherapy and proton therapy are under evaluation.     

Effect of scan projection radiography coverage on tube current modulation in pediatric and adult chest CT

PurposeTo investigate the effect of scan projection radiography (SPR) coverage on tube current modulation in pediatric and adult thoracic CT examinations.MethodsSixty pediatric and 60 adult chest CT examinations were retrospectively studied to determine the incidence rate of examinations involving SPRs that did not include the entire image volume (IV) or the entire primarily exposed body volume (PEBV). The routine chest CT acquisition procedure on a modern 64-slice CT system was imitated on five anthropomorphic phantoms of different size. SPRs of varying length were successively acquired. The same IV was prescribed each time and the computed tube current modulation plan was recorded. The SPR boundaries were altered symmetrically by several steps of ±10 mm with respect to the IV boundaries.ResultsThe upper IV boundary was found to be excluded from SPR in 52% of pediatric and 40% adult chest CT examinations. The corresponding values for the lower boundary were 15% and 20%, respectively. The computed tube current modulation was found to be considerably affected when the SPR did not encompass the entire IV. SPR deficit of 3 cm was found to induce up to 46% increase in the computed tube current value to be applied during the first tube rotations over lung apex.ConclusionsThe tube current modulation mechanism functions properly only if the IV set by the operator is entirely included in the localizing SPR image. Operators should cautiously set the SPR boundaries to avoid partial exclusion of prescribed IV from SPRs and thus achieve optimum tube current modulation.     

Volumetric Intensity-Modulated Arc Stereotactic Radiosurgery Boost in Oligometastatic Patients with Spine Metastases: a Dose-escalation Study

AimsTo report the final results of a dose-escalation study of volumetric intensity-modulated arc stereotactic radiosurgery (VMAT-SRS) boost after three-dimensional conformal radiation therapy in patients with spine metastases.Materials and methodsOligometastatic cancer patients bearing up to five synchronous metastases (visceral or bone, including vertebral ones) and candidates for surgery or radiosurgery were considered for inclusion. 25 Gy was delivered in 10 daily fractions (2 weeks) to the metastatic lesion, affected vertebrae and adjacent ones (one cranial and one caudal vertebra). Sequentially, the dose to spinal metastases was progressively increased (8 Gy, 10 Gy, 12 Gy) in the patient cohorts. Dose-limiting toxicities were defined as any treatment-related non-hematologic acute adverse effects rated as grade ≥3 or any acute haematological toxicity rated as ≥ 4 by the Radiation Therapy Oncology Group scale.ResultsFifty-two lesions accounting for 40 consecutive patients (male/female: 29/11; median age: 71 years; range 40–85) were treated from April 2011 to September 2020. Most patients had a primary prostate (65.0%) or breast cancer (22.5%). Thirty-two patients received 8 Gy VMAT-SRS boost (total BED _α/β10: 45.6 Gy), 14 patients received 10 Gy (total BED _α/β10: 51.2 Gy) and six patients received 12 Gy (total BED _α/β10: 57.6 Gy). The median follow-up time was over 70 months (range 2–240 months). No acute toxicities > grade 2 and no late toxicities > grade 1 were recorded. The overall response rate based on computed tomography/positron emission tomography–computed tomography/magnetic resonance was 78.8%. The 24-month actuarial local control, distant metastases-free survival and overall survival rates were 88.5%, 27.1% and 90.3%, respectively.ConclusionA 12 Gy spine metastasis SRS boost following 25 Gy to the affected and adjacent vertebrae was feasible with an excellent local control rate and toxicity profile.     

Incidence,characteristics, management and outcome of patients with follicular lymphoma with tumor epidural compression,a study on 22 cases

PurposeFollicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression.Material and methodsObservational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000–2021).ResultsBetween 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range = [1–216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47–90%) of patients. The median PFS was of 36 months (95% CI 24–NA) and 5 years OS estimate was 79% (95% CI 62–100%). Two patients developed a relapse at a second epidural site.ConclusionFL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.     

Radiation dose to the low axilla in patients treated for early-stage breast cancer by locoregional intensity-modulated radiotherapy (IMRT)

PurposeTo determine the dose received by the low axilla during locoregional radiotherapy (RT) for early-stage breast cancer and to assess the impact of the treatment technique (three-dimensional conformal radiotherapy (3D-CRT) or rotational IMRT (VMAT) or helical tomotherapy (HT).Materials and methodsThe dosimetric study was performed on patients receiving normofractionated (NFRT - 50 Gy in 25 fractions) or hypofractionated (HFRT - 40 Gy in 15 fractions) locoregional radiotherapy (breast or chest wall and internal mammary, supraclavicular and infraclavicular nodes ± axillary nodes) by 3D-CRT or VMAT or HT at the Institut Curie Paris. Patients treated by breast-conserving surgery received a boost dose of 16 Gy and 10 Gy to the tumour bed, respectively.ResultsSixty-eight patients treated by RT from February 2017 to January 2019 were studied. The mean dose received by the low axilla when it was not part of the target volume was 30.8 Gy, 41.0 Gy and 44.4 Gy by 3D-CRT, VMAT and HT, respectively for NFRT and 24.2 Gy, 33.0 Gy and 34.9 Gy, respectively, for HFRT. With NFRT, 4.1% of the axilla received 95% (V95) of the prescribed dose by 3D-CRT compared to 24.5% and 33.6% by VMAT and HT, respectively; with HFRT, V95 was 3.9%, 19.5% and 24.1%, respectively.ConclusionThe axilla receives a non-negligible dose during locoregional radiotherapy; this dose is greater when VMAT or HT are used. Prospective studies must be conducted to assess the impact of this axillary dose in terms of morbidity, which currently remains unknown.     

Paramètres de radiosensibilité des cancers du sein

Breast cancers are highly radiosensitive since the risk of recurrences and of mortality after adjuvant radiotherapy following breast-conserving surgery is decreased by 15.7% and 3.8%, respectively at 10 years. The total dose if irradiation also significantly increases local control: a boost of 16 Gy to the tumour bed after breast-conserving surgery reduces the absolute risk of recurrence by 4% at 10 years. Breast cancers are sensitive to the dose per fraction, as shown by the results from four randomized trials which compared standard irradiation (50 Gy/25 fractions) with a hypofractionated scheme: no statistical difference was observed in locoregional recurrence and overall survival at 10 years. The α/β ratio, which reflects the dose per fraction and is theoretically over 10 Gy for tumour tissues, has been estimated between 2.2 and 4.4 Gy for breast cancers. Molecular abnormalities, such as overexpression of HER1 (especially in triple negative breast cancer) and HER2, induce a higher radioresistance. In vitro studies showed that targeted therapies, which block these receptors, increase breast cancer radiosensitivity. Tumour stem cells have been identified in breast cancers and are characterized by a higher radioresistance. This radioresistance could be related to a better repair of radiation-induced DNA damages and a decrease of reactive oxygen species (ROS), which are involved in their occurrence. In the future, a better understanding of genetics tumour abnormalities will allow to identify new radiosensitivity settings in breast cancers.     

In vitro effects of Trastuzumab Emtansine (T-DM1) and concurrent irradiation on HER2-positive breast cancer cells

BackgroundTo determine the effects of concurrent irradiation and T-DM1 on HER2-positive breast cancer cell lines.MethodsFive human breast cancer cell lines (in vitro study) presenting various levels of HER2 expression were used to determine the potential therapeutic effect of T-DM1 combined with radiation. The toxicity of T-DM1 was assessed using viability assay and cell cycle analysis was performed by flow cytometry after BrdU incorporation. HER2 cells were irradiated at different dose levels after exposure to T-DM1. Survival curves were determined by cell survival assays (after 5 population doubling times).ResultsThe results revealed that T-DM1 induced significant lethality due to the intracellular action of DM1 on the cell cycle with significant G2/M phase blocking. Even after a short time incubation, the potency of T-DM1 was maintained and even enhanced over time, with a higher rate of cell death. After irradiation alone, the D₁₀ (dose required to achieve 10% cell survival) was significantly higher for high HER2-expressing cell lines than for low HER2-expressing cells, with a linearly increasing relationship. In combination with irradiation, using conditions that allow cell survival, T-DM1 does not induce a radiosensitivity.ConclusionsAlthough there is a linear correlation between intrinsic HER2 expression and radioresistance, the results indicated that T-DM1 is not a radiation-sensitizer under the experimental conditions of this study that allowed cell survival. However, further investigations are needed, in particular in vivo studies before reaching a final conclusion.     

Stereotactic radiotherapy for hepatocellular carcinoma induced by hepatitis C and the relationships of changes in carbohydrate antigen 19-9 with AFP and PIVKA-II

PurposeAssessing the therapeutic effects of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) takes time. Purpose of our study was to explore the relationships of changes in carbohydrate antigen 19-9 (CA 19-9) with those in the existing markers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II).Patients and methodsThe subjects were 16 patients who underwent SBRT for solitary HCC ≤ 3 cm induced by hepatitis C between June 2016 and July 2019. Observation periods ranged from 8–43 (median: 28) months, ages from 59–85 (median: 65) years.ResultsChanges in CA 19-9 levels after SBRT were categorised into three patterns: 1) a transient elevation followed by a decline (75%); 2) a transient decline followed by an elevation (18.8%); and 3) no change (6.3%). Among patients showing a transient CA 19-9 elevation followed by a decline, which was the most frequent pattern, 75% showed these changes in synchronisation with AFP and preceded the changes in PIVKA-II, while in the other 25%, CA 19-9 changes were in synchronisation with PIVKA-II and preceded those in AFP. At the time of recurrence, 62.5% showed a continuous CA 19-9 elevation, either in synchronisation with other markers or by itself.ConclusionsThis is the first investigation of changes in CA 19-9 levels after SBRT for HCC induced by hepatitis C. Characteristic changes in CA 19-9, AFP, and PIVKA-II levels were observed as responses after treatment. As for its correlations with tumour markers, the acute responses of PIVKA-II tended to be slower than those of CA 19-9 and AFP. Although the sample size was small, our findings raise the possibility that measuring these 3 biomarkers after SBRT may be useful for monitoring patients for HCC recurrence.     

Hypofractionnement à visée curative dans le cancer de la prostate

Radiotherapy plays a central role in the management of localized prostate cancer, but the total duration of treatment of nearly 2 months poses not only problems of fatigue related to repetitive transports, especially for older patients, but also increases the overall cost of treatment including linear accelerators occupancy and patient transportation. To address this problem, various teams have developed hypofractionated radiotherapy protocols seeking to maintain the same efficacy and toxicity while reducing the total duration of treatment. These hypofractionated protocols require recent techniques such as image-guided radiation therapy (IGRT) and intensity-modulated radiation therapy (IMRT). Single centre series have validated the feasibility of “light” hypofractionation schemes at doses per fraction less than 6 Gy Similarly, different teams have shown the possibility of stereotactic irradiation for delivering “severe” hypofractionation schemes at doses greater than 6 Gy per fraction. Whatever the dose per fraction, the current clinical data support the conclusion that hypofractionated radiotherapy does not increase mid-term toxicity and could even improve biochemical control. Studies with the objective of demonstrating non-inferiority are expected to definitively validate the role of hypofractionated irradiation in the treatment of prostate cancer.     

Image-guided high-dose-rate interstitial brachytherapy boost in the radical radiotherapy for a huge metastatic carcinoma of cervical lymph nodes from an unknown primary site

The purpose of this article was to report the treatment effect of image-guided high-dose-rate interstitial brachytherapy boost in the radical radiotherapy for a huge metastatic carcinoma of cervical lymph nodes from an unknown primary site. The patient was a 75-year-old male. A diagnostic biopsy showed metastatic squamous cell carcinoma and the tumour size was 7.5 × 6.5 × 11.5 cm³ before treatment (N3; AJCC 7th). After external beam radiotherapy with a dose of 60 Gy in 30 fractions, the residual tumour (6.2 × 4.7 × 6.0 cm³) was treated with image-guided high-dose-rate interstitial brachytherapy boost under ultrasound guidance. The brachytherapy dose was 16 Gy in four fractions of 4 Gy each. Removal of the huge metastatic tumour was securely achieved by high dose rate interstitial brachytherapy guided with ultrasound scanning. The refractory tumour in the patients healed uneventfully after image-guided high-dose-rate interstitial brachytherapy without recurrence during the 24 months of follow-up. The image-guided high-dose-rate interstitial brachytherapy boost may be a proposed treatment strategy for metastatic carcinoma of cervical lymph nodes from an unknown primary site with radical radiotherapy, especially for huge residual tumour.     

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience

PurposeThe purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique.Patients and methodsIn a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined.ResultsThe median age of this series of 832 women was 61.5 years (range: 29–90 years). Various types of fractionation were used: 50 Gy in 25 fractions (17.9%), 66 Gy in 33 fractions (50 Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66 Gy in 33 fractions.) (46.5%), 40 Gy in 15 fractions or 41.6 Gy in 13 fractions (26.1%) and 30 Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P = 0.2). In this population of 36 patients, 28 (3.3%) had “in-breast” local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P < 0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P < 0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P = 0.14).ConclusionThe results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.     

Model-Based Selection for Proton Therapy in Breast Cancer: Development of the National Indication Protocol for Proton Therapy and First Clinical Experiences

AimsProton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences.Materials and methodsA national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy.ResultsThe model of Darby et al. (N Engl J Med 2013; 368:987–82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021.ConclusionThe NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands.     

Second invasive breast cancers in patients treated with breast-conserving therapy

ObjectiveSecond breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments.Methods168,427 patients with primary breast cancer who underwent BCT between 1990 and 2005 were identified in the SEER database. The risks of IBTR and CBC were estimated by annual hazard rate. The breast cancer-specific survival (BCSS) were assessed using multivariable Cox regression analysis.ResultsWith median follow-up of 13 years after BCT, 5413 patients developed an IBTR and 4050 patients had a CBC. The risk of IBTR peaked between 10 and 15 years after BCT, while the risk of CBC distributed evenly. 45.9% of IBTRs were classified as a TR and 54.1% as an NP. The time interval from primary breast cancer to NP was longer than to TR and CBC (P < 0.001). Patients with TR had a poorer BCSS than NP (P = 0.003) and CBC (P = 0.002). There was no difference in BCSS between mastectomy and repeat BCT for treating TR (P = 0.584) or NP (P = 0.243). The BCSS of CBCs treated with BCT was better than mastectomy (P = 0.010). Chemotherapy didn't improve the survival of patients with TR (P = 0.058). However, TRs with grade III or negative hormone receptors benefited from chemotherapy significantly.ConclusionPatients with TR had a poorer BCSS than NP and CBC. Classifying IBTR may provide clinical significance for treatments.     

A new method to optimize resection area using a radiation treatment planning system and deformable image registration for breast-conserving surgery after neoadjuvant chemotherapy

BackgroundWe devised a breast-conserving surgery (BCS) utilizing a new image-processing and projection technique using a radiation treatment planning system (RTPS) and deformable image registration (DIR) for patients with breast cancer after neoadjuvant chemotherapy (NAC). RTPSs and DIR are commonly used in planning radiation treatment. The purpose of this pilot study was to evaluate the feasibility of our procedure.Patients and methodsTwenty-six patients diagnosed with breast cancer underwent NAC and BCS between November 2014 and May 2020. Multidetector-row computed tomography was performed in the same position used for surgery before and after NAC. In the DIR, CT before NAC was fused to CT after NAC. The RTPS simulated the design of tumor excision, and excision area was projected onto the breast skin utilizing an irradiation device.ResultsIn 26 patients with breast cancer after NAC, BCS was performed using the processing and projection technique of the RTPS with DIR. Only 1 of 26 patients showed carcinoma present in the surgical margins, and subsequently developed ipsilateral breast tumor recurrence. Mean excised volume was 33.5 cm³ (range, 12.8–62.8 cm³), and percent breast volume excised was 6.8% (range, 2.5–15.7%).ConclusionsThis pilot study confirmed the simplicity and utility of our procedure for minimally invasive BCS in patients with breast cancer after NAC. We will keep evaluating the safety and efficacy of our procedure in more patients.