Difference between planned and delivered radiotherapy dose to the internal mammary nodes in high-risk breast cancer patients.

Background and purpose: Chest wall movement during radiotherapy can impact the delivered dose to the internal mammary nodes (IMN) in high-risk breast cancer patients. Using portal imaging and dose reconstruction we aimed to examine the delivered IMN dose coverage. Material and methods: Cine MV images were recorded for 39 breast cancer patients treated with daily image-guided radiotherapy (IGRT) in deep-inspiration breath-hold (DIBH). On the final frame of each cine MV recording the chest wall was matched with the Digitally Reconstructed Radiograph (DRR) from the treatment plan. The geometrical chest wall error was determined in the imager-plane perpendicular to the cranio-caudal direction, rounded to integer millimeters, and binned. For each 1 mm bin, an isocenter-shifted treatment plan was recalculated assuming that the projected error observed in the cine MV image was caused by anterior-posterior chest wall movement in the IMN region. A weighted plan sum yielded the IMN clinical target volume receiving at least 90% dose (V90_CTVn_IMN). Results: The mean number of cine MV observations per patient was 36 (range 26-55). Most patients (67%) had on average a posterior chest wall position at treatment compared to planned. This translated into a change in the delivered median V90_CTVn_IMN of -0.7% (range, -11.9-2.9%; p < 0.001). The V90_CTVn_IMN reduction was greater than 9% in three patients. No clinically relevant differences were found for the mean lung dose or mean heart dose. Conclusion: Using cine MV images, we found that the delivered V90_CTVn_IMN was significantly lower than planned. In 8% of the patients, the V90_CTVn_IMN reduction exceeded 9%.

Clinical outcomes using a 3D printed tandem-needle-template and the EMBRACE-II planning aims for image guided adaptive brachytherapy in locally advanced cervical cancer.

BACKGROUND: Extensive local disease or narrow vagina may compromise brachytherapy (BT) in patients with cervical cancer. This is the first study to analyze long-term outcomes of using 3D printed vaginal tandem-needle templates (3DP TNT) for transvaginal insertion of needles in parallel (P) or parallel and oblique (P&O) direction to the tandem. MATERIAL AND METHODS: All patients treated with BT using 3DP TNT from 2015-2020 were included. Decision to use a 3DP TNT and preplanning were made after 4-5 weeks of external beam radiotherapy, based on gynecological examination and MRI with a tandem-ring applicator in situ. The TNT was 3D-printed in house consisting of a circular template with P&O holes for guidance of plastic needles and a shaft fitting the uterine tandem. Thus, the radioactive source was never in direct contact with the 3DP TNT. The TNT was 3D printed in a standard or personalized configuration. Planning aims were based on the Embrace II protocol. RESULTS: 101 patients (median age of 63 years) were included: 49 with P needles only and 52 with P&O needles. Personalized TNT was used in 19 patients in the P&O group. Performance status (WHO) was > 0 in 48%. FIGO2018 stage III-IV was present in 77%. T-score at diagnosis and BT was 9.1 and 6.3 respectively, with a significantly higher T-score in the P&O compared to P group. The mean high-risk CTV D90 was 93 Gy with no significant difference between the two groups. Three-year local control rates were 85%, 95%, 75% for the overall, P- and P&O group respectively and 68%, 80% and 56% for cancer specific survival. Grade ≥3 treatment related complications were observed in 10 (10%) patients. CONCLUSIONS: 3DP TNT for BT in cervical cancer provides successful management of very extensive local disease and/or unfavorable anatomy with the possibility for treatment individualization.

Characterization of combined intracavitary/interstitial brachytherapy including oblique needles in locally advanced cervix cancer.

PURPOSE: To characterize and report on dosimetric outcomes of image guided adaptive brachytherapy (IGABT) using intracavitary and interstitial (IC/IS) applicators including oblique needles (O-needles) in locally advanced cervical cancer (LACC). METHODS AND MATERIALS: Twenty LACC patients treated with radio-chemotherapy and offered IC/IS-IGABT including O-needles were analyzed. An in-house 3D-printed vaginal template was used to steer the needles parallel and obliquely in relation to the tandem, supplemented with free-hand needles if needed. Implant characteristics and loading patterns were analyzed. Using the equivalent dose in 2Gy-fractions (EQD2) concept, cumulative (EBRT+BT) V85, V75, V60Gy, targets/OARs doses and high dose volumes (150%, 200% and 300% (100% = 85 Gy EQD210)) were evaluated. RESULTS: Median(range) tumor width at diagnosis was 5.5(3.6; 7.5)cm; CTVHR volume was 45(23; 136)cm3 with maximum distance from tandem to CTVHR border of 3.4(2.5; 4.8)cm. T-stage distribution was IIB/III/IVA in 6(30%)/9(45%)/5(25%) of patients. At BT, 13(65%) patients had distal parametrial/pelvic wall infiltration. Median(range) number of needles per patient was 11(8-18). Average distribution of intrauterine, vaginal and interstitial dwell times were 31%, 25% and 44%, respectively. Median(range) dwell-time per dwell position was 11(2-127)% of average point-A based standard loading. Median V85Gy/V150%/V200%/V300% were 85(38; 171)/41(21; 93)/22(12; 41)/7(4; 19) cm3; CTVHR D90% was 93(83; 97)Gy EQD210; bladder/rectum/sigmoid/bowel D2cm3 were 78(64; 104)/65(52; 76)/59(53; 69)/61(47; 76)Gy EQD23. CONCLUSIONS: The use of O-needles in patients with large and/or unfavorable tumors resulted in excellent target coverage and OARs sparing. Intrauterine and vaginal loadings were reduced compared to standard loading and almost half of the loading was shifted into IS needles. This was achieved with gentle loading in the majority of dwell positions.

Does the combination of hyperthermia with low LET (linear energy transfer) radiation induce anti-tumor effects equivalent to those seen with high LET radiation alone?

INTRODUCTION: The combination of hyperthermia with low LET (linear energy transfer) radiation may have similar anti-tumor effects as high LET radiation alone. This pre-clinical study determined the optimal heating temperature and time interval between radiation and heat to achieve this equivalent effect. METHODS: C3H mammary carcinomas (200 mm3 in size) growing in the right rear foot of CDF1 mice was used in all experiments. Tumors were locally irradiated with graded doses of either 240 kV ortho- or 6 MV mega-voltage X-rays to produce full dose-response curves. Heating (41.0-43.5 °C; 60 min) was achieved by immersing the tumor bearing foot in a water-bath applied at the same time, or up to 4-hours after, irradiating. The endpoint was the percentage of mice showing local tumor control at 90 days, with enhancements calculated from the ratios of the radiation doses causing 50% tumor control (± 95% confidence intervals). RESULTS: Previous published results in this tumor model reported that carbon ions were 1.3-1.7 times more effective than low LET radiation at inducing tumor control. Similar enhancements occurred with a temperature of only 41.0 °C with a simultaneous heat and radiation treatment. However, higher temperatures were needed with the introduction of any interval; at 42.5 °C, the enhancement was 2.5 with a simultaneous treatment, decreasing to a value within the carbon ion range with a 4-hour interval. CONCLUSIONS: Combining hyperthermia with low LET radiation can be as effective as high LET at inducing tumor control, but the temperature needed depended on the time interval between the two modalities.

Fully automated detection of heart irradiation in cine MV images acquired during breast cancer radiotherapy.

PURPOSE: To develop robust automated detection of heart irradiation in continuous portal images (cine MV images) of tangential breast cancer treatments. METHODS: Cine MV images of 302 tangential field deliveries were recorded for ten left-sided breast cancer patients receiving deep-inspiration breath-hold radiotherapy. An algorithm for fully automated heart edge detection in cine MV images was developed and tested for all images. The algorithm first enhances the heart edge contrast greatly by exploiting that pixels on the heart edge change their intensity cyclically, and highly correlated, at 1-3 Hz due to heartbeat. The algorithm then detects the heart edge in the enhanced image and calculates the exposed heart area within the field aperture. RESULTS: The algorithm correctly identified the heart edge in all cine MV series with heart exposure (169 of 302 field deliveries). With conservative selection criteria the algorithm on average identified 70 heart edge pixels in the heart-including field deliveries (range: 10-230) without false positives. With less strict criteria 106 heart edge pixels were identified on average (range: 13-262) with 0.6% being false positives. The heart edge bordering the lung was segmented highly reliably even a few millimeters outside the field edge. For six patients with frequent heart irradiation, the exposed heart area showed large interfraction variations and smaller intrafraction variations. CONCLUSIONS: Automated heart edge detection in cine MV images was proposed, developed and shown to be highly efficient for heart exposure detection in tangential breast fields. It may allow unsupervised surveillance of heart exposure at all tangential breast cancer treatments in a clinic.

Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo.

INTRODUCTION: The aim of the present study was to examine the RBE for early damage in an in vivo mouse model, and the effect of the increased linear energy transfer (LET) towards the distal edge of the spread-out Bragg peak (SOBP). METHOD: The lower part of the right hind limb of CDF1 mice was irradiated with single fractions of either 6 MV photons, 240 kV photons or scanning beam protons and graded doses were applied. For the proton irradiation, the leg was either placed in the middle of a 30-mm SOBP, or to assess the effect in different positions, irradiated in 4 mm intervals from the middle of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system. RESULTS: The MDD50 values with 95% confidence intervals were 36.1 (34.2-38.1) Gy for protons in the middle of the SOBP for score 3.5. For 6 MV photons, it was 35.9 (34.5-37.5) Gy and 32.6 (30.7-34.7) Gy for 240 kV photons for score 3.5. The corresponding RBE was 1.00 (0.94-1.05), relative to 6 MV photons and 0.9 (0.85-0.97) relative to 240 kV photons. In the mice group positioned at the SOBP distal dose fall-off, 25% of the mice developed early skin damage compared with 0-8% in other groups. LETd,z = 1 was 8.4 keV/µm at the distal dose fall-off and the physical dose delivered was 7% lower than in the central SOBP position, where LETd,z =1 was 3.3 keV/µm. CONCLUSIONS: Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated.

Individualised 3D printed vaginal template for MRI guided brachytherapy in locally advanced cervical cancer.

Intracavitary-interstitial applicators for MRI guided brachytherapy are becoming increasingly important in locally advanced cervical cancer. The 3D printing technology enables a versatile method for obtaining a high degree of individualisation of the implant. Our clinical workflow is presented and exemplified by a stage IVA cervical cancer with superior dose distribution.