Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort.

PURPOSE: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. MATERIALS: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. RESULTS: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively. CONCLUSIONS: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.

Interpreting a rising prostate-specific antigen after brachytherapy for prostate cancer.

The aim of the present study was to review the English language literature on the topic of prostate-specific antigen bounce after brachytherapy and present a summary of the current knowledge. Although ultimately prostate-specific antigen is a reliable measure of success after prostate brachytherapy, it can be very misleading in the first 3 years because of the frequency with which temporary benign rises in prostate-specific antigen occur. We have reviewed the English language literature on the topic of prostate-specific antigen bounce under the following headings: prostate neoplasms, brachytherapy, biochemical definition of prostate-specific antigen failure, "benign prostate-specific antigen bounce" and "prostate-specific antigen spike". We included brachytherapy delivered as either low dose rate or high dose rate, and either as monotherapy or as a boost combined with external beam radiotherapy. A benign self-limited rise in prostate-specific antigen after prostate brachytherapy is seen in an average of 35% of patients, but increases in frequency with younger age. In patients aged less than 55 years, it is observed in up to 68%. Other factors, such as sexual activity, dose, prostate volume and the use of high dose rate versus low dose rate have been implicated in affecting the frequency of the benign bounce. Benign increases in prostate-specific antigen are frequent after prostate brachytherapy. It is important to recognize and correctly diagnose this phenomenon in order to avoid unnecessary salvage treatment.

Androgen deprivation therapy: minimizing exposure and mitigating side effects.

Despite common and occasionally serious side effects, androgen deprivation therapy (ADT) is widely used in the management of prostate cancer at all stages and presentations. ADT is frequently used in situations in which evidence of benefit is lacking, such as combined with definitive radiotherapy for favorable-risk prostate cancer, or in the primary management of elderly patients with low-risk disease. In intermediate- and high-risk disease, the role of ADT is being challenged and is decreasing in importance, as the ability to deliver very high biologically effective doses becomes more widely available, especially through the combination of external radiotherapy and brachytherapy. Appropriately selecting patients for ADT according to established indications will minimize the number exposed, whereas systematic patient education before initiating treatment can ameliorate the side effects. Minimizing the exposure to ADT and efforts to mitigate the side effects may have a beneficial effect on quality of life for many men with prostate cancer.

Low-dose Radiation Therapy in the Management of COVID-19 Pneumonia (LOWRAD-Cov19). Final results of a prospective phase I-II trial.

BACKGROUND AND PURPOSE: To evaluate the results of low-dose radiation therapy (LD-RT) to lungs in the management of patients with COVID-19 pneumonia. MATERIAL AND METHODS: We conducted a prospective phase I-II trial enrolling COVID-19 patients ≥50 years-old, with bilateral lung involvement at imaging study and oxygen requirement (oxygen saturation ≤93% on room air). Patients received 1 Gy to whole lungs in a single fraction. Primary outcome was a radiological response assessed as severity and extension scores at days +3 and +7. Secondary outcomes were toxicity (CTCAE v5.0), days of hospitalization, changes in inflammatory blood parameters (ferritin, lymphocytes, C-reactive protein, d-dimer and LDH) and SatO2/FiO2 index (SAFI), at day +3 and +7. Descriptive analyses were summarized as means with standard deviation (SD) and/or medians with interquartile ranges (IQR). A Wilcoxon sign rank test for paired data was used to assess the CT scores and Chi Square was used to assess for comparison of categorical variables. RESULTS: Forty-one patients were included. Median age was 71 (IQR 60-84). Eighteen patients (44%) previously received an anti-COVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids during LD-RT. The extension score improved significantly (p = 0.02) on day +7. Mean baseline extension score was 13.7 (SD ± 4.9) with a score of 12.2 (±5.2) at day 3, and 12.4 ± 4.7 at day 7. No differences were found in the severity score. SAFI improved significantly on day +3 and +7 (p < 0.01). Median SAFI on day 0 was 147 (IQR 118-264), 230 (IQR 120-343) on day +3 and 293 (IQR 121-353) on day +7. Significant decrease was found in C-reactive protein on day +7 (p = 0.02) and in lymphocytes counts on day +3 and +7 (p = 0.02). The median number of days in hospital after RT was 11 (range 4-78). With a median follow-up of 60 days after LD-RT, 26 (63%) patients were discharged, 11 (27%) died because of COVID respiratory failure and 4 (10%) died of other causes. CONCLUSIONS: LD-RT is a feasible and well-tolerated treatment that could lead to rapid clinical improvement. Large randomized trials would be required to establish the efficacy of LD-RT to treat COVID-19 pneumonia.

Low-Dose Radiation Therapy in the Management of Coronavirus Disease 2019 (COVID-19) Pneumonia (LOWRAD-Cov19): Preliminary Report.

PURPOSE: Low-dose radiation therapy (LD-RT) has been shown to have an anti-inflammatory effect, and preliminary results suggest it is feasible to treat patients with coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: We conducted a prospective, single-arm, phase 1/2 clinical trial enrolling patients aged ≥50 years, who were coronavirus disease 2019 (COVID-19) positive, at phase 2 or 3 with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Primary outcome was radiologic response using severity and extension score on baseline computed tomography (CT), at days 3 and 7 after LD-RT. Secondary outcomes were toxicity using Common Terminology Criteria for Adverse Events v.5.0, duration of hospitalization, blood work evolution, and oxygen requirements using SatO2/FiO2 index (SAFI), at days 3 and 7 after LD-RT. RESULTS: Nine patients were included. Median age was 66 (interquartile range, 57-77). Severity score was stable or decreased in the third CT but was not statistically significant (P = .28); however, there were statistically significant changes in the extension score (P = .03). SAFI index significantly improved 72 hours and 1 week after LD-RT (P = .01). Inflammatory blood parameters decreased 1 week after RT compared with baseline; only lactate dehydrogenase decreased significantly (P = .04). Two patients presented grade 2 lymphopenia after RT and another (with baseline grade 3) worsened to grade 4. Overall, the median number of days of hospitalization was 59 (range, 26-151). After RT the median number of days in the hospital was 13 (range, 4-77). With a median follow-up after RT of 112 days (range, 105-150), 7 patients were discharged and 2 patients died, 1 due to sepsis and the other with severe baseline chronic obstructive pulmonary disease from COVID-19 pneumonia. CONCLUSIONS: Our preliminary results show that LD-RT was a feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.

A phase II trial of less than 7 weeks of concomitant cisplatin-paclitaxel chemoradiation in locally advanced cervical cancer.

OBJECTIVES: This study was undertaken to determine the tolerability of a 7-week schedule of external beam radiation therapy, high-dose-rate brachytherapy, and weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of the cervix. METHODS: Twenty-nine patients with International Federation of Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40 mg/m per week of intravenous (i.v.) cisplatin and 50 mg/m per week of i.v. paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 30 Gy of high-dose-rate brachytherapy. RESULTS: Eleven patients (37.9%) were able to complete the 6 scheduled cycles of chemotherapy. The median number of weekly chemotherapy cycles administered was 5 (range, 2-7). Thirty-five (20.1%) of 174 cycles of chemotherapy were not given because of toxicity. The median dose intensity of cisplatin was 31 mg/m per week (95% confidence interval [CI], 25.2-36.8); that of paclitaxel was 44 mg/m per week (95% CI, 39.9-48.3). Twenty-two patients (78.6%) were able to complete the planned radiation course in less than 7 weeks. Median radiation treatment length was 45 days (95% CI, 43.4-46.6). After a median follow-up of 48 months, 7 patients (24.1%) experienced severe (Radiation Therapy Oncology Group grade 3 or higher) late toxicity. No fatal events were observed. Seven patients have failed, 1 locally and 6 at distant sites. The 8-year local/pelvic control rate was 95.7%, and the 8-year freedom from systemic failure rate was 76.1%. Eight-year actuarial disease-free survival and overall survival were 63.1% and 75.9%, respectively. CONCLUSIONS: This study demonstrated unacceptable toxicity of combining the stated doses of concurrent cisplatin and paclitaxel chemotherapy with definitive radiotherapy for patients with advanced cervical cancer. Additional phase I/II trials are recommended to clearly establish the recommended phase II dose for these drugs.

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer.

BACKGROUND: Pemetrexed is a multitargeted antifolate initially approved as a single agent for the second-line treatment of locally advanced or metastatic non-small cell lung cancer and more recently in the first-line setting combined with cisplatin. The combination of pemetrexed with carboplatin has been tested in several phase II clinical trials showing interesting antitumour activity with mild toxicity. Supplementation with folic acid and vitamin B12 during treatment with pemetrexed is recommended to reduce potential haematological and gastrointestinal adverse events. CASE REPORT: A patient experienced cutaneous lesions including widespread erythema, epidermal detachment, and skin denudation, associated with deterioration of his general condition after the second cycle of this chemotherapy combination, which was clinically and histologically compatible with toxic epidermal necrolysis (Lyell's syndrome). Treatment with systemic steroids, antihistamines, and antibiotics led to resolution of the skin lesions and improvement of his general condition. CONCLUSION: To our knowledge, this is the second case reported in the literature of this type of suspected adverse drug reaction associated with a pemetrexed-based chemotherapy combination.

Validation study of ultrasound-based high-dose-rate prostate brachytherapy planning compared with CT-based planning.

PURPOSE: The use of transrectal ultrasound (TRUS) to both guide and plan high-dose-rate (HDR) brachytherapy (BT) for prostate is increasing. Studies using prostate phantoms have demonstrated the accuracy of ultrasound (US) needle tip reconstruction compared with CT imaging standard. We have assessed the in vivo accuracy of needle tip localization by TRUS using cone-beam CT (CBCT) as our reference standard. METHODS AND MATERIALS: Needle positions from 37 implants have been analyzed. A median of 16 needles (range, 16-18) per implant were inserted, advanced to the prostate base, and their tips identified using live TRUS images and real-time planning BT software. Needle protrusion length from the template was recorded to allow for reverification before capturing images for planning. The needles remained locked in the template, which was fixed to the stepper, while a set of three-dimensional TRUS images was acquired for needle path reconstruction and HDR-BT treatment planning. Following treatment, CBCT images were acquired for subsequent needle reconstruction using a BT Treatment Planning System. The coordinates of each needle tip were recorded from the Treatment Planning System for CT and US and compared. RESULTS: A total of 574 needle tip positions have been compared between TRUS and CBCT. Of these, 59% agreed within 1 mm, 27% within 1-2 mm, and 11% agreed within 2-3 mm. The discrepancy between tip positions in the two modalities was greater than 3 mm for only 20 needles (3%). CONCLUSIONS: The US needle tip identification in vivo is at least as accurate as CT identification, while providing all the advantages of a one-step procedure.

Ultrasound-planned high-dose-rate prostate brachytherapy: dose painting to the dominant intraprostatic lesion.

PURPOSE: To demonstrate the feasibility of using high-dose-rate (HDR) brachytherapy to deliver 125% of the prescription dose to the dominant intraprostatic lesion (DIL) as defined on multiparametric MRI while respecting critical organ dose constraints. METHODS AND MATERIALS: Twenty-six patients with biopsy-proven predominantly unilateral prostate cancer consented to a university ethics-approved Phase 2 study of selective dose escalation. Combined information from endorectal T2 MRI sequences, dynamic contrast enhancement, and apparent diffusion coefficient maps was used to contour the DIL and prostate. Images were fused to intraoperative transrectal ultrasound for transposition of the DIL. Treatment consisted of two fractions of 10 Gy HDR brachytherapy to the entire prostate with 12.5 Gy to the DIL, combined with 46 Gy in 23 fractions of external beam radiotherapy. RESULTS: All patients had intermediate- or high-risk disease; 25 of 26 had a visible DIL (mean volume, 2.9 cm(3); SD, 1.8). Mean percentage of prostate receiving prescription dose (V100) was 98.1% (SD, 1.2). Mean dose to 90% of the DIL was 13.4 Gy (SD, 1.0). The coverage of the DIL was excellent with a mean of 95.7% (SD, 5.0) receiving the planned escalation of 25%. Established dose constraints to rectum and urethra were respected in all cases; where DIL coverage was limited by proximity to urethra or rectum, a mean dose to 90% of the DIL of 12.3 Gy was achieved. CONCLUSIONS: Modest dose escalation to the DIL (25-30%) using ultrasound-planned HDR brachytherapy is feasible for selected intermediate- and high-risk patients while respecting critical organ constraints and is achievable within the practice setting of a community cancer center.

Permanent seed brachytherapy for locally recurrent prostate cancer after radical prostatectomy: a case report and review of the literature.

PURPOSE: To describe the management of a patient with locally recurrent prostate cancer in the prostate bed, 10 years after a radical prostatectomy. METHODS AND MATERIALS: A 71-year-old man had a radical prostatectomy for a Gleason 7 clinical T2a carcinoma of the prostate in 2000. Final pathologic stage was pT3a pN0. Postoperatively his prostate-specific antigen was undetectable, but by 2008 it was 1.0ng/mL and in 2011 it reached to 1.43ng/mL. He was referred for consideration of salvage radiotherapy. Staging workup was negative but transrectal ultrasound revealed a 15cc recurrence in the prostate bed. A combination of external beam radiation therapy (4600/23/4.5 weeks to the pelvis) and a brachytherapy boost (115Gy) was selected for definitive management. Androgen ablation was not used. RESULTS: The treatment was well tolerated. The brachytherapy boost was planned in a similar fashion to a de novo implant for an intact prostate. The postimplant dosimetry was evaluated using magnetic resonance imaging-computed tomography (MR-CT) fusion and appeared satisfactory. Acute toxicity was minimal. Six months after brachytherapy, the prostate-specific antigen had fallen from 1.43 to 0.05ng/mL. CONCLUSIONS: Dose escalation with combined external beam and brachytherapy may be feasible if recurrent disease can be visualized using transrectal ultrasound and encompassed in an implanted volume. Although longer followup and a larger series of patients are required to demonstrate safety and efficacy, consideration should be given this approach.