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.

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.

NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction.

BACKGROUND: In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. MATERIAL AND METHODS: Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction α/ß = 3 Gy was used and the USC parameters used were: α/ß = 3 Gy, D(0) = 1.0 Gy, [Formula: see text] = 10, α = 0.206 Gy(-1) and d(T) = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether "high doses to small volumes" or "low doses to large volumes" are most important for lung toxicity. RESULTS AND DISCUSSION: NTCP analysis with the LKB-model using parameters m = 0.4, D(50) = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D(50) = 20 Gy n = 0.93 with LQ correction and n = 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ,USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling.

Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.

PURPOSE: The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study. PATIENTS AND METHODS: Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume. RESULTS: Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027). CONCLUSION: With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.

Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study.

BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.

Dummy run for a phase II study of stereotactic body radiotherapy of T1-T2 N0M0 medical inoperable non-small cell lung cancer.

In forthcoming multicentre studies on stereotactic body radiotherapy (SBRT) compliance with volume and dose prescriptions will be mandatory to avoid unnecessary heterogeneity bias. To evaluate compliance in a multicentre setting we used two cases from an ongoing phase II study of SBRT of T1-T2N0M0 inoperable NSCLC in a dummy run oriented on volumes and doses. Six Scandinavian centres participated. Each centre received CT-scans covering the whole lung volumes of two patients with instructions to follow the study protocol when outlining tumour and target volumes, prescribing doses and creating dose plans. Volumes and doses of the 12 dose plans were evaluated according to the study protocol. For the two patients the GTV volume range was 24 to 39 cm3 and 26 to 41 cm3, respectively. The PTV volume range was 90 to 116 cm3, and 112 to 155 cm3, respectively. For all plans the margin between CTV and PTV in all directions followed in detail the protocol. The prescribed dose was for all centres 45 Gy/3 fractions (isocentre dose about 66 Gy). The mean GTV doses ranged from 63 to 67 Gy and from 63 to 68 Gy, respectively. The minimum doses for GTV were between 50-64 Gy and between 55-65 Gy, respectively. The dose distribution was conformed to PTV for 10 of 12 plans and 2 of 12 plans from one centre had sub-optimal dose distribution. Most of the volume and dose parameters for the participating centres showed fully acceptable compliance with the study protocol.

Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma.

BACKGROUND AND PURPOSE: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated in the present phase-II trial. PATIENTS AND METHODS: Twenty-two patients with locally advanced and surgically non-resectable, histological proven pancreatic carcinoma were included into the trial. The patients were immobilized by the Elekta stereotactic body frame (SBF) or a custom made body frame. SRT was given on standard LINAC with standard multi-leaf collimator. Central dose was 15 Gyx3 within 5-10 days. RESULTS: Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction. Only two patients (9%) were found to have a partial response (PR), the remaining had no change (NC) or progression (PD) after treatment. Six patients had local tumour progression, but only one patient had an isolated local failure without simultaneous distant metastasis. Median time to local or distant progression was 4.8 months. Median survival time was 5.7 months and only 5% were alive 1 year after treatment. Acute toxicity reported 14 days after treatment was pronounced. There was a significant deterioration of performance status (P=0.008), more nausea (P=0.001) and more pain (P=0.008) after 14 days compared with base-line. However, 8 of 12 patients (66%) improved in performance status, scored less nausea, pain, or needed less analgesic drugs at 3 months after treatment. Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach. CONCLUSIONS: SRT was associated with poor outcome, unacceptable toxicity and questionable palliative effect and cannot be recommended for patients with advanced pancreatic carcinoma.