Stereotactic ablative radiotherapy for oligometastatic prostate cancer.

Background: The present study assessed clinical outcomes of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer patients. Materials and methods: Between 2017 and 2020, 37 lesions (12 osseous and 25 nodal targets) detected with conventional and/or functional imaging, were treated in 29 patients (pts), in different clinical settings: de novo oligometastatic (2 pts), oligorecurrent castration-sensitive (19 pts), castration-resistant (6 pts) prostate cancers and oligoprogressive disease during systemic therapy (2 pts). SBRT was delivered with volumetric modulated arc therapy up to a total dose of 21 Gy given in 3 fractions for bone and 30 Gy in 5 fractions for nodal metastases. A total of 34% of pts received hormonal therapy. We evaluated biochemical control [prostate serum antigen (PSA) increase < 10%)], progression free-survival (PFS) (time from SBRT to biochemical progression), local control (LC) (time from SBRT to in-field radiologic progression), hormone/systemic therapy-free survival, acute and late toxicities. Results: At 3 months, biochemical response was observed in 20/29 pts (69%). At a median follow-up of 17 months (range 6-33), 8/20 (40%) of the 3-month responders remained free from progression. Two-year PFS and LC were 37% and 70%, respectively. In-field progression occurred in 3/37 (8%) lesions. Hormone/systemic therapy was delayed by an average of 11.6 months (range 3-28). No significant difference in PFS based on the type of lesion or concomitant endocrine therapy was observed and no toxicity > grade 2 was reported. Conclusions: SBRT for oligometastatic prostate cancer offers a good biochemical/local control and tangible delay of hormone/systemic therapy without major toxicities.

A randomized clinical study on the impact of Comprehensive Geriatric Assessment (CGA) based interventions on the quality of life of elderly, frail, onco-hematologic patients candidate to anticancer therapy: protocol of the ONCO-Aging study.

BACKGROUND: Age is considered as one of the most important risk-factor for many types of solid and hematological cancers, as their incidence increases with age in parallel to the ever-growing elderly population. Moreover, cancer incidence is constantly increasing as a consequence of the increase in life expectancy that favors the process of cellular senescence. Geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In particular, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. Due to their frailty, elderly patients may be often under-treated and a therapeutic choice based also on a comprehensive geriatric assessment (CGA) is recommended. With these premises, we aim to test the impact of the CGA based interventions on the quality of life (QoL) of frail elderly onco-hematological patients, identified by the G8 screening, candidate for innovative target directed drugs or treatments including the combination of radiotherapy and chemotherapy (RT + CT). METHODS: Patients aged > 65 years, candidate to target directed agents or to RT + CT treatments are screened for frailty by the G8 test; those patients classified as frail (G8 ≤ 14) are randomized to receive a CGA at baseline or to conventional care. The primary endpoint is QoL, assessed by EORTC QLQ-C30C. As collateral biological study, the potential prognostic/predictive role of T-cell senescence and myeloid derived suppressor cells (MDSC) are evaluated on plasma samples. DISCUSSION: This trial will contribute to define the impact of CGA on the management of frail elderly onco-hematologic patients candidate to innovative biological drugs or to integrated schedules with the association of RT + CT. Furthermore, the use of plasma samples to assess the potential prognostic value of imbalance of immune-competent cells is expected to contribute to the individualized care of elderly patients, resulting into a fine tuning of the therapeutic strategies. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04478916 . registered July 21, 2020 - retrospectively registered.

Tumour seeding in the surgical pathway after resection of skull base chordoma.

AIM: The aim of this study is to review the clinical series in which tumour seeding was reported after skull base surgery for chordomas. BACKGROUND: The occurrence of implantation of cancer cells during surgical procedures for the removal of chordoma is a rare event described by a number of authors in a few patient series and case reports. MATERIALS AND METHODS: Literature search was performed by PubMed and Scopus by using the words "surgical tumour seeding, tumour implantation, surgical pathway recurrence, skull base chordoma, and clivus chordoma". RESULTS: Six retrospective series and 7 case reports were included in the analysis. In total, 34 patients are described with pathway recurrence, 30 at a single site and 4 at multiple sites. In the 5 largest chordoma series, the rate of occurrence of surgical seeding ranged from 1.3% to 7.3% (3.9%). In the 34 patients diagnosed with tumour seeding, the most frequent surgical approach was trans-nasal/trans-sphenoidal, that was used in 12 cases. The median time from primary treatment to surgical pathway tumour seeding ranged from 7 to 78 months. Data of the treatment of seeding are available in 26/34 patients. All of them underwent a new surgery, 6 received additional external beam radiotherapy, and 2 intraoperative radiotherapy. CONCLUSIONS: The risk of surgical seeding should be taken into consideration when deciding on the surgical approach and the planning treatment volume for postoperative radiation therapy. The surgical pathway should be included in follow-up studies to diagnose this peculiar type of treatment failure possibly at an early phase.

Review of photon and proton radiotherapy for skull base tumours.

An extremely large variety of benign and malignant tumours occur at skull base; these tumour lesions are in the proximity to structures deputed to relevant physiologic functions, limiting extensive surgical approaches to this body district. Most recent progresses of surgery and radiotherapy have allowed to improve local control with acceptable rates of side effects. Various photon radiotherapy techniques are employed, including 3-dimensional conformal radiotherapy, intensity modulated radiotherapy (IMRT), stereotactic radiotherapy (SRT) and brachytherapy that is manly limited to the treatment of primary or recurrent nasopharyngeal carcinoma. Proton beam radiotherapy is also extensively used thanks to its physical characteristics. Our review, focusing in particular on meningioma, chordoma, and chondrosarcoma, suggests that proton therapy plays a major role in the treatment of malignant tumours whereas photon therapy still plays a relevant role in the treatment of benign tumour lesions.

Capecitabine-Induced Ileitis during Neoadjuvant Pelvic Radio-Chemotherapy for Locally Advanced Rectal Cancer: A Case Report with Literature Review.

We report on a clinical case of capecitabine-induced acute ileitis in a patient treated with pre-operative concurrent chemoradiation with capecitabine for locally advanced rectal cancer and provide a comprehensive literature review. This a rare, but life-threatening, clinical situation, that clinicians should be aware of. Severe persistent diarrhea is the most frequent clinical feature and computed tomography is a valid tool for diagnosis. Conservative management includes capecitabine withdrawal, antidiarrheal therapy and endovenous hydration, together with dietary modifications and broad-spectrum antibiotics. Pelvic irradiation represents an adjunctive risk factor, which may increase the likelihood of occurrence of terminal ileitis. Early recognition and prompt intervention are crucial for successful clinical management.

Ultra-Hypofractionation for Whole-Breast Irradiation in Early Breast Cancer: Interim Analysis of a Prospective Study.

We report on the early clinical outcomes of a prospective series of early breast cancer (EBC) patients treated with ultra-hypofractionated post-operative whole-breast irradiation (WBI) after breast-conserving surgery (BCS) and axillary management. Primary endpoints were patient's compliance and acute toxicity. Secondary endpoints included physician-rated cosmesis and ipsilateral breast tumour recurrence (IBTR). Acute toxicity was evaluated at the end of WBI, 3 weeks and 6 months thereafter, according to the Common Terminology Criteria for Adverse Events (v. 5.0). Patients were treated between September 2021 and May 2022. The treatment schedule for WBI consisted of either 26 Gy in 5 fractions over one week (standard approach) or 28.5 Gy in 5 fractions over 5 weeks (reserved to elders). Inverse planned intensity-modulated radiation therapy (IMRT) was used employing a static technique. A total of 70 patients were treated. Fifty-nine were treated with the 26 Gy/5 fr/1 w and 11 with the 28.5 Gy/5 fr/5 ws schedule. Median age was 67 and 70 in the two groups. Most of the patients had left-sided tumours (53.2%) in the 26 Gy/5 fr/1 w or right-sided lesions (63.6%) in the 28.5 Gy/5 fr/5 ws group. Most of the patients had a clinical T1N0 disease and a pathological pT1pN0(sn) after surgery. Ductal invasive carcinoma was the most frequent histology. Luminal A intrinsic subtyping was most frequent. Most of the patients underwent BCS and sentinel lymph node biopsy and adjuvant endocrine therapy. All patients completed the treatment program as planned. Maximum detected acute skin toxicities were grade 2 erythema (6.7%), grade 2 induration (4.4%), and grade 2 skin colour changes. No early IBTR was observed. Ultra-hypofractionated WBI provides favourable compliance and early clinical outcomes in EBC after BCS in a real-world setting.

18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment.

PURPOSE: [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis prediction in different tumors, but its role in esophageal cancer is still debated. The aim of this study was to evaluate the role of semiquantitative baseline PET parameters as possible prognostic and predictive factors in a series of esophageal carcinomas treated with combined modalities. METHODS: 43 patients with esophageal carcinoma were treated with chemoradiotherapy (CRT) followed by surgery in 20 cases and underwent pre-treatment 18F-FDG-PET/CT. Semiquantitative PET parameters were evaluated including Standardized Uptake Value (SUVmax e SUVmean), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) with isocontour of 41 and 50%. Further variables analyzed were gender, primary tumor site, histological type, use of surgery, achievement of a radical resection and the type of chemotherapy regimen. The correlation of all variables with treatment response, loco-regional control (LR), Overall survival (OS) and Disease-Free Survival (DFS) was evaluated. RESULTS: SUVmax, SUVmean50 and SUVmean41 were significantly higher in node-positive cases and in squamous cell carcinomas. With respect to prognostic factors, MTV was found to be correlated with OS: patients with MTV41 < 11.32 cm3 and MTV50 < 8.07 cm3 (both p values = 0.04) showed better 3-year OS rates (33 vs. 20%). Further factors predicting a better prognosis were the use of surgery and radical resection (R0) (both p values < 0.01). CONCLUSIONS: Pre-treatment MTV values were significant prognostic factors for OS, together with the use of surgery and R0 resection in esophageal cancers treated with multimodal therapies.

Targeted Next-Generation Sequencing for the Identification of Genetic Predictors of Radiation-Induced Late Skin Toxicity in Breast Cancer Patients: A Preliminary Study.

Normal tissue radiosensitivity is thought to be influenced by an individual's genetic background. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we carried out targeted next-generation sequencing of germline DNA samples from 48 breast cancer patients with extreme late skin toxicity phenotypes, consisting of 24 cases with grade 2-3 subcutaneous fibrosis and/or grade 2-3 telangiectasia (LENT-SOMA scales) and 24 controls with grade 0 fibrosis and grade 0 telangiectasia. In this exploratory study, a total of five single-nucleotide variants (SNVs) located in three genes (TP53, ERCC2, and LIG1) reached nominal levels of statistical significance (p < 0.05). In the replication study, which consisted of an additional 45 cases and 192 controls, none of the SNVs identified by targeted NGS achieved nominal replication. Nevertheless, TP53 rs1042522 (G > C, Pro72Arg) in the replication cohort had an effect (OR per C allele: 1.52, 95%CI: 0.82-2.83, p = 0.186) in the same direction as in the exploratory cohort (OR per C allele: 4.70, 95%CI: 1.51-14.6, p = 0.007) and was found be nominally associated to the risk of radiation-induced late skin toxicity in the overall combined cohort (OR per C allele: 1.79, 95%CI: 1.06-3.02, p = 0.028). These results raise the possibility of an association between TP53 rs1042522 and risk of radiation-induced late skin toxicity in breast cancer patients; however, large replication studies are warranted for conclusive evidence.

Running a Radiation Oncology Department at the Time of Coronavirus: An Italian Experience.

Starting from Wuhan, China, SARS-CoV-2 has been a catastrophic epidemic involving many countries worldwide. After China, Italy has been heavily affected, and severe measures to limit the spread of the virus have been taken in the last weeks. Radiation oncology departments must guarantee optimal cancer treatments even in such a challenging scenario of an ongoing aggressive epidemic. Adopted preventive measures and recommendations are highlighted for patients, professionals, and clinical operations to minimize the risk of infection while safely treating patients with cancer.

Running a Radiation Oncology Department at the Time of Coronavirus: An Italian Experience.

Starting from Wuhan, China, SARS-CoV-2 has been a catastrophic epidemic involving many countries worldwide. After China, Italy has been heavily affected, and severe measures to limit the spread of the virus have been taken in the last weeks. Radiation oncology departments must guarantee optimal cancer treatments even in such a challenging scenario of an ongoing aggressive epidemic. Adopted preventive measures and recommendations are highlighted for patients, professionals, and clinical operations to minimize the risk of infection while safely treating patients with cancer.

Adaptive Strategy for External Beam Radiation Therapy in Prostate Cancer: Management of the Geometrical Uncertainties With Robust Optimization.

PURPOSE: We aim to develop and validate a new adaptive method for prostate cancer radiation therapy (RT), using an offline strategy to improve treatment personalization by modeling the internal target volume on individual basis and account for the residual set-up uncertainties by robust optimization. METHODS AND MATERIALS: Twenty patients with intermediate-high prostate cancer treated with radical radiation therapy were enrolled. The first step of the offline adaptive RT strategy is the identification of a patient-specific internal target volume based on the kV cone beam computed tomography (kV-CBCT) data sets acquired during the first 5 fractions. The deformable image registration algorithm ANACONDA was used to propagate the clinical target volumes (CTVs) from the reference-planning computed tomography to the CBCTs; these contours were assessed by a radiation oncologist. In the second step, the internal target volume was used to replan the treatment using a min-max robust algorithm based on the worst scenario optimization. The CTV coverage and organs-at-risk sparing achieved with the robust plan (RP) were analyzed and compared with the original standard plan, calculating the dose distributions on the residual CBCTs. RESULTS: The RP was shown to achieve optimal coverage of the CTV even in the worst scenario, with significantly lower doses to the rectum and bladder. CTV coverage of the RP was statistically better than the standard plan in terms of D99 (P = .008) and D98 (P = .02). Statistically significant mean dose reduction and D2 reduction were noted for the rectum (P < .05) and bladder (P < .009). Moreover, the RP appeared to be less sensitive to bladder and rectal filling. CONCLUSIONS: This adaptive strategy in prostate cancer radiation therapy is feasible and safe; it may be used to adapt the treatment with better target coverage and organs-at-risk sparing than standard planning target volume-based planning.

Radiotherapy in COVID-19 patient affected by multiple myeloma: a case report.

In COVID-19 pandemic, cancer patients may be vulnerable for their immunological status and need of immunosuppressive anti-neoplastic treatments. Choosing the best treatment option in COVID-19 positive cancer patients is still a challenging issue. We report the case of a 62-year-old woman diagnosed with multiple myeloma and affected by COVID-19. After the diagnosis of multiple myeloma in January 2019, the patient underwent first line therapy followed by bone marrow autologous stem cell transplantation, achieving a complete response in September 2019. In March 2020, the patient showed intrathoracic progression of the disease, resulting in a severe dysphagia and concomitant positivity to SARS-CoV-2 swab test, cough, fever, and dyspnea related to the involvement of the lung parenchyma as shown by CT-scan. After her admittance to a COVID-19 dedicated inward, she was administered oral hydroxychloroquine and darunavir-cobicistat for 7 days with stabilization of her general clinical conditions. For the worsening of dysphagia, after multidisciplinary discussion, it was decided to deliver radiotherapy to the mediastinal and paravertebral mass with 8 Gy single fraction. After 5 days, her clinical conditions improved, with reduction of dysphagia. The CT confirmed a partial response with reduction of the mass of about 50%. Viral clearance was confirmed by triple negative search for SARS-CoV-2 on nasopharyngeal swabs, one month after first documentation of positivity. Unfortunately, the patient died three months later due to a pulmonary mycotic infection causing respiratory failure. To our knowledge, this case report describes the first experience of mediastinal radiotherapy in a COVID-19 patient affected by myeloma reported in the literature. In case of clinical indication, even in presence of SARS-CoV-2 infection, radiotherapy can be safely delivered and might be considered a treatment option as shown by our experience in this challenging case of intrathoracic myeloma.