Impact of inter-observer variability on first axillary level dosimetry in breast cancer radiotherapy: An AIRO multi-institutional study.

This study quantified the incidental dose to the first axillary level (L1) in locoregional treatment plan for breast cancer. Eighteen radiotherapy centres contoured L1-L4 on three different patients (P1,2,3), created the L2-L4 planning target volume (single centre planning target volume, SC-PTV) and elaborated a locoregional treatment plan. The L2-L4 gold standard clinical target volume (CTV) along with the gold standard L1 contour (GS-L1) were created by an expert consensus. The SC-PTV was then replaced by the GS-PTV and the incidental dose to GS-L1 was measured. Dosimetric data were analysed with Kruskal-Wallis test. Plans were intensity modulated radiotherapy (IMRT)-based. P3 with 90° arm setup had statistically significant higher L1 dose across the board than P1 and P2, with the mean dose (Dmean) reaching clinical significance. Dmean of P1 and P2 was consistent with the literature (77.4% and 74.7%, respectively). The incidental dose depended mostly on L1 proportion included in the breast fields, underlining the importance of the setup, even in case of IMRT.

Prognostic Score in Radiotherapy Practice for Palliative Treatments (PROPHET) Study for Bone Metastases: An Investigation Into the Clinical Effect on Treatment Prescription.

Purpose: Bone metastases frequently occur during malignant disease. Palliative radiation therapy (PRT) is a crucial part of palliative care because it can relieve pain and improve patients' quality of life. Often, a clinician's survival estimation is too optimistic. Prognostic scores (PSs) can help clinicians tailor PRT indications to avoid over- or undertreatment. Although the PS is supposed to aid radiation oncologists (ROs) in palliative-care scenarios, it is unclear what type of support, and to what extent, could impact daily clinical practice. Methods and Materials: A national-based investigation of the prescriptive decisions on simulated clinical cases was performed in Italy. Nine clinical cases from real-world clinical practice were selected for this study. Each case description contained complete information regarding the parameters defining the prognosis class according to the PS (in particular, the Mizumoto Prognostic Score, a validated PS available in literature and already applied in some clinical trials). Each case description contained complete information regarding the parameters defining the prognosis class according to the PS. ROs were interviewed through questionnaires, each comprising the same 3 questions per clinical case, asking (1) the prescription after detailing the clinical case features but not the PS prognostic class definition; (2) whether the RO wanted to change the prescription once the PS prognostic class definition was revealed; and (3) in case of a change of the prescription, a new prescriptive option. Three RO categories were defined: dedicated to PRT (RO-d), nondedicated to PRT (RO-nd), and resident in training (IT). Interviewed ROs were distributed among different regions of the country. Results: Conversion rates, agreements, and prescription trends were investigated. The PS determined a statistically significant 11.12% of prescription conversion among ROs. The conversion was higher for the residents and significantly higher for worse prognostic scenario subgroups, respectively. The PS improved prescriptive agreement among ROs (particularly for worse-prognostic-scenario subgroups). Moreover, PS significantly increased standard prescriptive approaches (particularly for worse-clinical-case presentations). Conclusions: To the best of our knowledge, the PROPHET study is the first to directly evaluate the potential clinical consequences of the regular application of any PS. According to the Prophet study, a prognostic score should be integrated into the clinical practice of palliative radiation therapy for bone metastasis and training programs in radiation oncology.

Conventional and Algorithmic Music Listening before Radiotherapy Treatment: A Randomized Controlled Pilot Study.

Music listening is a widespread approach in the field of music therapy. In this study, the effects of music listening on anxiety and stress in patients undergoing radiotherapy are investigated. Sixty patients with breast cancer who were candidates for postoperative curative radiotherapy were recruited and randomly assigned to three groups: Melomics-Health (MH) group (music listening algorithmically created, n = 20); individualized music listening (IML) group (playlist of preferred music, n = 20); no music group (n = 20). Music listening was administered for 15 min immediately before simulation and during the first five radiotherapy sessions. The State-Trait Anxiety Inventory (STAI) and the Psychological Distress Inventory (PDI) were administered before/after treatment. Cochran's Q test and McNemar test for paired proportions were performed to evaluate if the proportion of subjects having an outcome score below the critical value by treatment and over time was different, and if there was a change in that proportion. The MH group improved in STAI and PDI. The IML group worsened in STAI at T1 and improved STAI-Trait at T2. The IML group worsened in PDI at T2. The No music group generally improved in STAI and PDI. Clinical and music listening-related implications are discussed defining possible research perspectives in this field.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Radiotherapy for oligometastatic cancer: a survey among radiation oncologists of Lombardy (AIRO-Lombardy), Italy.

AIMS: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy. METHODS AND STUDY DESIGN: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics. RESULTS: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5-10 Gy (8/13) using schedules of 3-5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT. CONCLUSIONS: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC.

Target position reproducibility in left-breast irradiation with deep inspiration breath-hold using multiple optical surface control points.

The aim of this study was to investigate the use of 3D optical localization of multiple surface control points for deep inspiration breath-hold (DIBH) guidance in left-breast radiotherapy treatments. Ten left-breast cancer patients underwent whole-breast DIBH radiotherapy controlled by the Real-time Position Management (RPM) system. The reproducibility of the tumor bed (i.e., target) was assessed by the position of implanted clips, acquired through in-room kV imaging. Six to eight passive fiducials were positioned on the patients' thoraco-abdominal surface and localized intrafractionally by means of an infrared 3D optical tracking system. The point-based registration between treatment and planning fiducials coordinates was applied to estimate the interfraction variations in patients' breathing baseline and to improve target reproducibility. The RPM-based DIBH control resulted in a 3D error in target reproducibility of 5.8 ± 3.4 mm (median value ± interquartile range) across all patients. The reproducibility errors proved correlated with the interfraction baseline variations, which reached 7.7 mm for the single patient. The contribution of surface fiducials registration allowed a statistically significant reduction (p < 0.05) in target localization errors, measuring 3.4 ± 1.7 mm in 3D. The 3D optical monitoring of multiple surface control points may help to optimize the use of the RPM system for improving target reproducibility in left-breast DIBH irradiation, providing insights on breathing baseline variations and increasing the robustness of external surrogates for DIBH guidance.

One-step intraoperative radiotherapy optimizes conservative treatment of breast cancer with advantages in quality of life and work resumption.

BACKGROUND: Intraoperative radiotherapy (IORT) could be not-inferior to external beam radiotherapy (EBRT) in selected patients, but toxicities, self-perception of body image, quality of life, and resumption of work or daily activities have been poorly explored. The aim of the present study was to compare these outcomes between EBRT, IORT full-dose (IORT-f) and IORT boost (IORT-b). METHODS: 443 consecutive patients, candidates for breast-conserving surgery, were included: EBRT was performed in 220 patients (49.7%), IORT-f in 140 patients (31.6%), and IORT-b in 83 patients (18.7%). Radiotherapy-related toxicities were registered. Patients were evaluated at 6 months for Body Image after Breast Cancer Questionnaire (BIBCQ) to assess possible changes in self-perception of body image and limitations. A second questionnaire explored the impact of EBRT, IORT-f and IORT-b on resumption of work and normal daily activities. RESULTS: EBRT had a higher risk of breast fibrosis and retraction (OR 3.58, 95% CI 1.024-12.526, p = 0.046) and breast edema (OR 6, 95% CI 2.077-17.335, p = 0.001) compared to IORT-f, but a lower risk of seroma compared to IORT-b (OR 0.36, 95% CI 0.166-0.785, p = 0.01). The BIBCQ scores showed a better outcome in arm concerns with IORT-f (-3.3) vs. IORT-b (-1.3, p = 0.002) and EBRT (-1.7, p = 0.006), although biased by the lower rate in axillary dissections. Return to daily activities occurred after 70.6 days with EBRT vs. 41 days with IORT-f (p < 0.0001) and 53.3 days with IORT-b (p = 0.07), without any effect of age or axillary dissection. CONCLUSION: IORT could reduce adverse effects, allowing faster resumption of job and houseworks.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Reproducibility of the external surface position in left-breast DIBH radiotherapy with spirometer-based monitoring.

Deep inspiration breath hold (DIBH) in left-sided breast cancer radiotherapy treatments allows for a reduction in cardiac and pulmonary doses without compromising target coverage. The selection of the most appropriate technology for DIBH monitoring is a crucial issue. We evaluated the stability and reproducibility of DIBHs controlled by a spirometric device, by assessing the variability of the external surface position within a single DIBH (intra-DIBH) and between DIBHs performed in the same treatment session (intrafraction) or in different sessions (interfraction). The study included seven left-breast cancer patients treated with spirometer-based DIBH radiotherapy. Infrared optical tracking was used to record the 3D coordinates of seven to eleven passive markers placed on the patient's thoraco-abdominal surface during 29-43 DIBHs performed in six to eight treatment sessions. The obtained results showed displacements of the external surface between different sessions up to 6.3mm along a single direction, even at constant inspired volumes. The median value of the interfraction variability in the position of breast passive markers was 2.9 mm (range 1.9-4.8 mm) in the latero-lateral direction, 3.6 mm (range 2.2-4.6mm) in the antero-posterior direction, and 4.3mm (range 2.8-6.2 mm) in the cranio-caudal direction. There were no significant dose distribution variations for target and organs at risk with respect to the treatment plan, confirming the adequacy of the applied clinical margins (15 mm) to compensate for the measured setup uncertainties. This study demonstrates that spirometer-based control does not guarantee a stable and reproducible position of the external surface in left-breast DIBH radiotherapy, suggesting the need for more robust DIBH monitoring techniques when reduced margins and setup uncertainties are required for improving normal tissue sparing and decreasing cardiac and pulmonary toxicity.

Second malignancies following breast cancer treatment: a case-control study based on the Peridose methodology. Allegro project (task 5.4).

AIMS AND BACKGROUND: To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. MATERIAL AND STUDY DESIGN: A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose. RESULTS: 195 second cancers were registered (19% [corrected] of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was -3.15 cGy (range, -15.8 cGy and +2.7 cGy). CONCLUSIONS: The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.

Comparison between intensified neoadjuvant treatment and standard preoperative chemoradiation for rectal cancer.

OBJECTIVES: The aim of the current study was to compare a neoadjuvant regimen containing oxaliplatin with standard preoperative treatment for rectal cancer. METHODS: From December 2006 to December 2007, 20 patients with rectal cancer were treated at our Institution with the weekly addition of oxaliplatin (50 mg/m(2)) to radiotherapy (50.4-54.0 Gy in 28-30 daily fractions) and continuous infusion of 5-fluorouracil (200 mg/m(2)). The results of the regimen were compared with a historical control group including 21 consecutive patients previously treated with standard 5-fluorouracil treatment from December 2004 to October 2006. RESULTS: Both the rate of sphincter preservation in low rectal cancer (91.7% vs 36.4%, P = 0.009) and the rate of downstaging (84.2% vs 47.6%, P = 0.023) were higher in the oxaliplatin group than in the control group. Pathological complete response was achieved in 8 patients (42.1%) in the oxaliplatin group and in 4 patients (19.0%) in the control group (P = 0.172). When ypT0-pT1 stages were analyzed together, the P value was 0.051. Acute toxicity was increased in the oxaliplatin group, with a higher incidence of G3 diarrhea and pelvic pain than in the control group (30.0% vs 14.3%, P = NS). CONCLUSIONS: Our data seem to correlate the addition of oxaliplatin to the standard treatment for rectal cancer with higher rates of sphincter preservation, down-staging and complete response. Toxicity is increased and requires careful monitoring. However, our results refer to a retrospective comparison of a small series of patients and need to be validated by the large, phase III randomized trial currently ongoing.