Positron emission tomography for staging locally advanced cervical cancer and assessing intensity modulated radiotherapy approach.

AIMS: To evaluate toxicity and outcome of concomitant chemotherapy and intensity modulated radiotherapy (IMRT) with 18-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) based simultaneous integrated boost (SIB) of locally advanced cervical cancer (LACC). METHODS: Patients with LACC underwent chemo-radiation with IMRT and SIB. Staging and follow-up were performed with clinical evaluation and CT, MRI, 18FDG-PET/CT. SIB was done on positive nodes with 18FDG-PET/CT based planning. CT-based planning high-dose-rate brachytherapy (HDR-BT) was delivered as subsequent boost to the primary tumor. Cisplatin concomitant chemotherapy was administered during IMRT. RESULTS: Fourteen patients with cervical cancer were prospectively recruited between August 2014 and June 2017, 13 (93%) had a LACC, one (7%) patient was not evaluable because 18FDG-PET/CT evidenced metastases to the liver undetected by previous CT/MRI. Patients had a median age of 59 years, a median Karnofsky performance status of 100%, and a prevalence of squamous cell carcinoma histology (85%). SIB was delivered on 23 positive lymph nodes. IMRT median dose to the pelvis was 48.6 Gy in 27 fractions, SIB median dose 54 Gy in 27 fractions, HDR-BT boost median dose 21 Gy in 3 fractions. After a median follow-up of 30 months, 2-year local control and distant control were 86% and 86%, respectively. There were no grade 4 acute and/or late toxicities. CONCLUSIONS: The 18FDG-PET/CT influenced stage assessment and RT treatment planning due to its high specificity in distant metastases and nodal involvement detection. The IMRT with SIB for positive nodes was an effective therapy with acceptable toxicity in LACC.

STereotactic Ablative RadioTherapy in NEWly Diagnosed and Recurrent Locally Advanced Non-Small Cell Lung Cancer Patients Unfit for ConcurrEnt RAdio-Chemotherapy: Early Analysis of the START-NEW-ERA Non-Randomised Phase II Trial.

PURPOSE: This is a single arm phase 2 trial (Clinical trials.gov NCT05291780) to assess local control (LC) and safety of SAbR in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) unfit for concurrent chemo-radiation therapy (ChT-RT). METHODS: Neoadjuvant ChT was prescribed in fit patients. The tumor volume included primary tumor and any regionally positive node/s. The coprimary study endpoints were LC and safety. RESULTS: Between December 31, 2015, and December 31, 2020, 50 patients with LA-NSCLC were enrolled. Histology was squamous cell carcinoma and adenocarcinoma (ADC) in 52% and 48%, respectively. Forty (80%) patients had ultracentral tumor. Twenty-seven (54%) received neoadjuvant ChT and 7 (14%) adjuvant durvalumab. Median prescribed dose was 45 Gy (range, 35-55) and 40 Gy (35-45) in 5 daily fractions to tumor and node/s, respectively. After a median follow-up of 38 months (range, 12-80), 19 (38%) patients had experienced local recurrence (LR) at a median time of 13 months (range, 7-34). The median LR-free survival (FS) was not reached (95% confidence interval [CI], 28 to not reached). The 1-, 2-, and 3-year LR-FS rates were 86% ± 5%, 66% ± 7%, and 56% ± 8%, respectively. At last follow-up, 33 (66%) patients were alive. Median overall survival (OS) was 55 months (95% CI, 43-55 months). The 1-, 2-, and 3-year OS rates were 94% ± 3%, 79% ± 6%, and 72% ± 7%, respectively. No patients developed ≥ grade (G) 3 toxicity. ADC (hazard ratio [HR], 3.61; 95% CI, 1.15-11.35) was a significant predictor of better LC, while OS was significantly conditioned by smaller planning target volumes (HR, 1.004; 95% CI, 1.001-1.010) and tumor, node, and metastasis stage (HR, 4.8; 95% CI, 1.34-17). CONCLUSIONS: Patients with LA-NSCLC treated with SABR had optimal LC and promising OS in absence of ≥G3 toxicity. Our early outcomes would suggest the feasibility of using this approach in patients with LA-NSCLC unfit for concurrent ChT-RT.

Reliability of algebraic sum to evaluate adjuvant pelvic radiotherapy and vaginal cuff brachytherapy cumulative doses in uterine cancers.

Purpose: To evaluate the reliability of algebraic sum with respect to rigid fusion of treatment plans related to adjuvant external beam pelvic radiotherapy (APR) and vaginal cuff high-dose-rate brachytherapy (BT) in uterine cancer patients. Material and methods: For algebraic sum, APR and BT doses were mathematically added. Rigid fusion was realized overlapping computed tomography (CT) images of APR and BT treatment plans. Rectum and bladder were considered reference organs at risk (OARs). Following dose (D) parameters were examined: Dmax (0.5 cc), D20% and D50% for rectum, Dmax (0.5 cc) and D50% for bladder; for each parameter, differences between the two adopted methods were reported as Δ-values. Results: Twenty uterine cancer patients submitted to radical surgery followed by APR plus vaginal cuff BT were reviewed. APR was done with a dose of 25 × 2 Gy. All patients also receveid a vaginal cuff boost with BT at the dose of 2 × 5 Gy. Differences between mean cumulative doses calculated with rigid fusion and algebraic sum were evaluated. For the rectum and bladder ΔD50%, there were no significant differences, and BT contribution resulted minimal. An apparent significant difference value was registered in bladder ΔDmax (0.5 cc). No toxicity was observed. Conclusions: In uterine cancer patients submitted to APR and vaginal cuff BT, algebraic sum and rigid plan fusion of doses allowed to obtain similar results in evaluating cumulative OARs' doses. Further investigations and increased number of patients are recommended to confirm our findings.

Treatment of recurrent glioblastoma with stereotactic radiotherapy: long-term results of a mono-institutional trial.

AIMS AND BACKGROUND: Few clinical data exist concerning normal brain tissue tolerance to re-irradiation. The present study evaluated long-term outcome of 22 recurrent glioblastoma patients re-irradiated with radiosurgery or fractionated stereotactic radiotherapy. METHODS: Twenty-two patients were treated with radiosurgery (13, 59%) or fractionated stereotactic radiotherapy (9, 41%) for 24 lesions of recurrent glioblastoma. The male/female ratio was 14:8, median age 55 years (range, 27-81), and median Karnofsky performance status 90 (range, 70-100). The majority of the cases (77%) was in recursive partitioning analysis classes III or IV Radiosurgery or fractionated stereotactic radiotherapy was chosen according to lesion size and location. RESULTS: Median time between primary radiotherapy and re-irradiation was 9 months. Median doses were 17 Gy and 30 Gy, whereas median cumulative normalized total dose was 141 Gy and 98 Gy for radiosurgery and fractionated stereotactic radiotherapy, respectively. All patients submitted to radiosurgery had a cumulative normalized total dose of more than 100 Gy, whereas only a few (44%) of fractionated stereotactic radiotherapy patients had a cumulative normalized total dose exceeding 100 Gy. Median follow-up from re-irradiation was 54 months. At the time of analysis, all patients had died. After re-irradiation, 1 (4%) lesion was in partial remission, 16 (67%) lesions were stable, and the remaining 7 (29%) were in progression. Median duration of response was 6 months, and median survival from re-irradiation 11 months. Three of 13 (23%) patients submitted to radiosurgery developed asymptomatic brain radionecrosis. The cumulative normalized total dose for the 3 patients was 122 Gy, 124 Gy, and 141 Gy, respectively. In one case, the volume of the lesion was large (14 cc), and in the other 2 the interval between the first and second cycle of radiotherapy was short (5 months). CONCLUSIONS: Re-irradiation with radiosurgery and fractionated stereotactic radiotherapy is feasible and effective in recurrent glioblastoma patients. Apart from the importance of an accurate patient selection, cumulative radiotherapy dose and a correct indication for radiosurgery or fractionated stereotactic radiotherapy must be taken into account to avoid brain toxicity.

Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients.

OBJECTIVE: To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer. METHODS: 37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS). RESULTS: Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/ß ratio 10 Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity. CONCLUSION: SBRT was effective and safe in lung cancer adrenal metastases. A dose-response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies. ADVANCES IN KNOWLEDGE: SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.

Accelerated partial-breast irradiation with high-dose-rate brachytherapy: Mature results of a Phase II trial.

PURPOSE: The purpose of this study was to report mature clinical and cosmetic results of accelerated partial-breast irradiation with interstitial multicatheter high-dose-rate brachytherapy (HDR-BRT) in patients with early breast cancer. METHODS AND MATERIALS: 133 patients were recruited in a Phase II trial of exclusive HDR-BRT. Inclusion criteria were age ≥40 years, PS 0-2, unifocal invasive ductal cancer, intraductal cancer component <25%, negative axillary nodes, and tumor size ≤2.5 cm. Treatment schedule was 4 Gy twice a day up to a total dose of 32 Gy in eight fractions. RESULTS: Median age was 67 years (range, 42-85). There were 7 (5%) pT1a, 48 (36%) pT1b, 72 (54%) pT1c, and 6 (5%) pT2. Estrogen and progesterone receptors were positive in 119 (89%) and 93 (70%) patients, respectively. The median followup was 110 months (range, 12-163). After HDR-BRT, there were 3 (2%) in-field breast recurrences and 1 (1%) out-field breast recurrence. 5 (4%) patients developed contralateral breast cancer, another one (1%) isolated regional relapse in axillary node and 3 (2%) distant progression of disease. 19 (14%) patients reported a second primary cancer. 5-, 10-, and 13-year overall survival and cancer-specific survival were 95% and 100%, 84.5% and 100%, and 81.4% and 100%, respectively. Cosmetic outcome was excellent in 80% of cases. Late toxicity was significantly related to the skin administered doses (≤55% vs. > 55% of the prescribed dose, p < 0.05). CONCLUSIONS: Accelerated partial-breast irradiation delivered with HDR-BRT in selected patients with breast cancer was associated to high local control and survival with excellent cosmetic outcomes overall when skin dose was ≤55%.

A prospective phase II trial on reirradiation of brain metastases with radiosurgery.

PURPOSE: In our previous published trial on radiosurgery (SRS) of recurrent brain metastases (BM) after whole brain radiotherapy (WBRT), Karnofsky performance status (KPS) and administered dose conditioned outcome and late toxicity, respectively. Brain radionecrosis was registered in 6% of patients. With the aim to obtain similar satisfactory outcomes and limit toxicity, we started a phase II trial in which reirradiation of BM with SRS were done using a tighter patient selection. MATERIALS AND METHODS: Patients with BM recurring after WBRT were recruited for reirradiation with SRS. Only patients with good KPS (≥70), good neurologic functional score (NFS 0-1) and lesions with a diameter ≤20 mm were considered eligible for retreatment. Dose exceeding 20 Gy was never administered. RESULTS: The 59 patients reirradiated had 109 BM with a diameter range of 6-20 mm. Median interval between prior WBRT and SRS was 15 months and median SRS administered dose was 18 Gy (range 10-20 Gy). Complete and partial response (CR, PR) was obtained in 42% of patients with 2 years of control rate of 81%. Median overall survival (OS) after reirradiation was 14 months. No radionecrosis was detected. CONCLUSIONS: Analysis of our current trial compared with results of our previous data suggests that a tighter patient selection (KPS ≥ 70; NFS 0-1, BM with ≤20 mm of diameter) and SRS dose ≤20 Gy allowed a high OS rate, a good percentage of CR and PR which last for >2 years, and no brain radionecrosis.

Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study.

PURPOSE: We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy. METHODS: 240 patients received APBI (4Gy, twice daily; total dose 32Gy). RESULTS: Median follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6-4.3) and 6.6% (95%CI: 2.7-12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72). CONCLUSIONS: APBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.

Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer.

PURPOSE: To report our experience on high-dose-rate brachytherapy (HDR-BT) in patients with stage I-III endometrial cancer unfit to surgery. MATERIAL AND METHODS: Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95), median Karnofsky performance status 90% (range, 60-100). Histology was endometrial adenocarcinoma in 14 (82%), and non-endometrial in 3 (18%) patients. In 15 (88%) patients, clinical stage was I and in remaining 2 (12%) was III. All patients were evaluated with computed tomography (CT) and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC) was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression. RESULTS: Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT) combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131), 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS) at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adenocarcinoma) LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma) was 100% at 1 and 6 years (p = 0.05). Two (12%) patients had G2 acute toxicity and two others (12%) G1 late toxicity. CONCLUSIONS: Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection), it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology.

Lung reirradiation with stereotactic body radiotherapy.

PURPOSE: We examined safety and efficacy of stereotactic body radiotherapy (SBRT) in reirradiation for lung recurrent lesions (LRLs). MATERIALS AND METHODS: Eighteen patients, 4 with lung local failure from primary non-small cell lung carcinomas and 14 with lung metastases, were reirradiated with SBRT for 29 LRLs. Doses were recalculated to an Equivalent Dose of 2 Gy per fraction (EQD2) and α/ß ratio was assumed to be Gy10 for primary and metastatic lung tumors and Gy3 for organ at risk. Cumulative administered doses were calculated adding doses of prior radiotherapy and reirradiation. RESULTS: Peripherally located lesions received 5 fractions of 8-10 Gy, while centrally ones lower doses (5 fractions of 5-8 Gy). Cumulative EQD2 did not exceed 198 Gy10 and reirradiated volumes were rather small (median 18 cc). Local control was obtained for all patients except one and lasted medially 43 months. Median overall survival was 40 months from reirradiation. Only acute grade 1 toxicity was recorded. CONCLUSIONS: Reirradiation of LRLs with SBRT was feasible and effective. It is important to appropriately select patient and to adopt organ at risk constrains considering cumulative doses.

Re-irradiation of brain metastases and metastatic spinal cord compression: clinical practice suggestions.

The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy. Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50-60 Gy in 2 Gy daily fractions. New metastases appear in 22-73% of the cases after whole brain radiotherapy, but the percentage of reirradiated patients is 3-10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status > 70, age < 65 years, controlled primary and no extracranial metastases are those with the best prognosis. The absence of extracranial disease was the most significant factor in conditioning survival, and maximum tumor diameter was the only variable associated with an increased risk of unacceptable acute and/or chronic neurotoxicity. Re-treatment of brain metastases can be done with whole brain radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy. Most patients had no relevant radiation-induced toxicity after a second course of whole brain radiotherapy or stereotactic radiosurgery. There are few data on fractionated stereotactic radiotherapy in the re-irradiation of brain metastases. In general, the incidence of an "in-field" recurrence of spinal metastasis varies from 2.5-11% of cases and can occur 2-40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment, length of the irradiated spinal cord, and age of the treated animals influence the risk of radiation-induced myelopathy. An alpha/beta ratio of 1.9-3 Gy could be generally the reference value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy, the linear-quadratic equation become a less valid model. The early diagnosis of relapse is crucial in conditioning response to re-treatment.

Operator exposure to x-ray in left and right radial access during percutaneous coronary procedures: OPERA randomised study.

OBJECTIVE: Left radial access (LRA) and right radial access (RRA) have been shown to be safe and effective for coronary arteries catheterisation. However, the differences between the two approaches in terms of radiation exposure are still unclear. The aim of the present investigation is to evaluate in a randomised study, the dose of radiation absorbed by operators using either LRA or RRA. DESIGN: Randomised, prospective, double arm, single centre study. SETTING: University Hospital. PATIENTS: Male or female subjects with stable, unstable angina and silent ischaemia. INTERVENTIONS: The present study is a comparison of LRA and RRA for coronary artery catheterisation in terms of operators' radiation exposure. MAIN OUTCOME MEASURES: The primary outcome measure was the radiation dose absorbed by operators; secondary outcome measures were fluoroscopy time, dose-area product and contrast delivered. RESULTS: A total of 413 patients were enrolled; 209 were randomly selected to undergo diagnostic procedures with RRA and 204 with LRA. The operator's radiation exposure was significantly lower in the left radial group (LRA 33±37 µSv vs RRA 44±32 µSv, p=0.04). No significant differences were observed in  fluoroscopy time (LRA 349±231s vs RRA 370±246 s p=0.09) and dose-area product (LRA 7011.42±3617.30 µGym(2) vs RRA 7382.38±5226.61 µGym(2), p=0.80), even though in both there was a trend towards a lower level in the LRA. No differences were observed in contrast medium delivered (LRA 89.92±32.55 ml vs RRA 88.88±35.35 ml, p=0.45). CONCLUSIONS: The LRA was associated in the present report with a lower radiation dose absorbed by the operator during coronary angiography.