Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

CITK Loss Inhibits Growth of Group 3 and Group 4 Medulloblastoma Cells and Sensitizes Them to DNA-Damaging Agents.

Medulloblastoma (MB) is the most common malignant brain tumor in children, and it is classified into four biological subgroups: WNT, Sonic Hedgehog (SHH), Group 3 and Group 4. The current treatment is surgery, followed by irradiation and chemotherapy. Unfortunately, these therapies are only partially effective. Citron kinase protein (CITK) has been proposed as a promising target for SHH MB, whose inactivation leads to DNA damage and apoptosis. D283 and D341 cell lines (Group 3/Group 4 MB) were silenced with established siRNA sequences against CITK, to assess the direct effects of its loss. Next, D283, D341, ONS-76 and DAOY cells were treated with ionizing radiation (IR) or cisplatin in combination with CITK knockdown. CITK depletion impaired proliferation and induced cytokinesis failure and apoptosis of G3/G4 MB cell lines. Furthermore, CITK knockdown produced an accumulation of DNA damage, with reduced RAD51 nuclear levels. Association of IR or cisplatin with CITK depletion strongly impaired the growth potential of all tested MB cells. These results indicate that CITK inactivation could prevent the expansion of G3/G4 MB and increase their sensitivity to DNA-damaging agents, by impairing homologous recombination. We suggest that CITK inhibition could be broadly associated with IR and adjuvant therapy in MB treatment.

Prostate cancer management at an Italian tertiary referral center: does multidisciplinary team meeting influence diagnostic and therapeutic decision-making process? A snapshot of the everyday clinical practice.

BACKGROUND: Multidisciplinary team (MDT) management decision-making process appears as an interesting tool to answer most aspects of prostate cancer (PCa) diagnosis and treatment, allowing a fairer choice of therapies. The aim of this study to prospectively investigate the impact on prostate cancer clinical management of the uro-oncology MDT meeting at an Italian tertiary referral center. METHODS: All cases discussed over an 18-months period at San Luigi Hospital uro-oncology MDT were prospectively evaluated for the impact of the MDT discussion on PCa clinical decision-making. Dilemma and management plan in the monodisciplinary visit before and/or after primary treatment were recorded. Subsequently, the MDT discussed the case and reached a consensus decision, which was also recorded. Changes in diagnostic assessment and patient management from pre- to post-MDT meeting were evaluated by a consultant urologist. RESULTS: Overall, 201 patients, of which 99, 81 and 21 with local, advanced and metastatic disease respectively, were selected for MDT evaluation. The most frequent reasons for MDT approach after either PCa diagnosis or primary treatment were metastatic disease or locally advanced disease/positive surgical margins/biochemical recurrence, respectively. Patients with local, advanced and metastatic disease had a significative change of diagnostic/therapeutic management in 23.2%, 46.9% and 33.4%, respectively (P<0.001). Multimodal treatment was recommended in 25.3%. CONCLUSIONS: The uro-oncology MDT meeting alters management plans in at least one-quarter of patients reaching almost 50% of cases in locally advanced disease.

Role of radiotherapy in improving activity of immune-modulating drugs in advanced renal cancer: Biological rationale and clinical evidences.

In the last few years, immune checkpoint inhibitors have been extensively investigated in renal cell carcinoma and led to remarkable results. Radiation therapy may increase the activity of immune modulating agents through different mechanisms, priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. Preclinical studies reported increased loco-regional control when radiation is combined with immune-checkpoint blockade. Moreover, increased systemic disease control has been demonstrated when local radiation is combined with both anti-CTLA-4 and anti-PD-1/PD-L1 inhibitors. Actually, several trials are ongoing testing the activity of radiation therapy in combination with different immune-modulating agents for the treatment of metastatic renal cell carcinoma. The aim of this paper is to focus on the biological rationale of adding radiation therapy to immune-modulating agents in renal cell carcinoma and to review the currently available clinical evidence about the combination of radiotherapy and immunotherapy.

Is Karnofsky Performance Status Correlate with Better Overall Survival in Palliative Conformal Whole Brain Radiotherapy? Our Experience.

AIM: Brain metastases (BMs) are a common event in the progression of many human cancers. The aim of this study was to evaluate the potential prognostic factors for the clinical identification of a subgroup of patients that could benefit from whole brain conformal radiotherapy (WBRT). MATERIALS AND METHODS: From January 2010 to February 2014, 80 patients with a diagnosis of BMs underwent WBRT at our Radiation Oncology Department, San Luigi Hospital, Italy. Among them, 36 medical records were retrospective reviewed. Gender, age, Karnofsky performance status (KPS), number of BMs on computed tomography and/or magnetic resonance images, presence or absence of perilesional edema, presence or absence of necrosis pattern, and histology of primary tumor were analyzed. Univariate and multivariate analyses were performed. RESULTS: In our cohort of patients, significant prognostic factors for 20 months overall survival was KPS> 70, while a statistical trend (P = 0.098) was registered regarding primary breast. CONCLUSION: WBRT can be still considered a standard and effective treatment in patients with BMs. High KPS and breast cancer primary tumor seem to be useful parameters for characterize a subgroup of patients with more favorable prognosis.

Volumetric and positional changes of planning target volumes and organs at risk using computed tomography imaging during intensity-modulated radiation therapy for head-neck cancer: an "old" adaptive radiation therapy approach.

PURPOSE: This study aimed to assess, in a department of radiation oncology not equipped with in-room imaging systems, volumetric and positional changes of planning target volumes (PTVs) and organs at risk in head and neck (H&N) cancer patients treated with intensity-modulated radiation therapy (IMRT), using consecutive off-board computed tomography (CT) imaging. Dosimetric aspects were not investigated. MATERIALS AND METHODS: Ten patients with H&N cancer underwent CT re-scanning at 3, 5, and 7 weeks. Positional changes of the PTVs and parotid glands as distances relative to the virtual isocentre were determined. The parotids glands (PGs) were re-delineated on each CT set and volume differences were computed. Anterior-posterior (AP) and latero-lateral (LL) displacements for the spinal cord at C1 and C6 level were calculated. Changes in patient body contours were evaluated by comparing the volumes within the external skin outline. RESULTS: Apart from two patients requiring re-planning due to substantial weight loss, our results evidenced no significant shifts of PTVs and PGs. PG volume decreased with a trend in volume reduction for the ipsilateral parotid. No significant shift of spinal cord at C1 and C6 level was detected, in either the AP or LL direction. The collected data demonstrated a trend in external skin contour volume loss. CONCLUSIONS: Our preliminary results reflect the literature data and indicate that an off-line adaptive RT approach is appropriate in clinical practice.

A case of primary mediastinal Ewing's sarcoma / primitive neuroectodermal tumor presenting with initial compression of superior vena cava.

Ewing's sarcomas and peripheral primitive neuroectodermal tumors (ES/PNETs) are high grade malignant neoplasms. These malignancies are characterized by a chromosome 22 rearrangement, arise from bone or soft tissue, predominantly affect children and young adults, and are grouped in the Ewing family of tumors. Multimodality treatment programs are the treatment of choice. Primary localization of ES/PNET in the mediastinum is extremely rare. We describe a case of ES/PNET presenting as a mediastinal mass with tracheal compression and initial signs of superior vena cava in a 66-year-old woman.

Should radiotherapy after primary systemic therapy be administered with the same recommendations made for operable breast cancer patients who receive surgery as first treatment? A critical review.

Primary systemic therapy is not only used in patients with locally advanced inoperable non-metastatic breast cancer but also for operable stage II and III cancer aimed at breast conservation. The indications for local-regional radiotherapy for patients who receive primary systemic therapy are still evolving. The purpose of this article is to provide a comprehensive discussion of how primary systemic therapy in operable breast cancer patients could affect the indications of radiotherapy to optimize local-regional treatment. An overview of available literature data regarding neoadjuvant treatment and radiotherapy is analyzed and discussed. Considering the variability of data on this issue, an appropriate approach could still be to tailor treatment decision to the individual clinical case.

Radiotherapy alone or with concomitant daily low-dose carboplatin in locally advanced, unresectable head and neck cancer: definitive results of a phase III study with a follow-up period of up to ten years.

AIM AND BACKGROUND: Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial. MATERIALS AND METHODS: From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin. RESULTS: The 3, 5 and 10-year local-regional recurrence-free survival rates were better in arm II (21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs. 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04). CONCLUSIONS: Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial.

Radiotherapy-induced taste impairment.

Changes in taste perception occur in a significant proportion of cancer patients. Among cancer patients treated with radiotherapy (RT) in head and neck area, the vast majority reports an altered taste sense during and after treatments. Taste impairment starts a few weeks after the beginning of irradiation, and almost all such patients experienced loss of taste acuity at a dose of 60 Gy. Some studies investigated the four basic taste intensities (sweet, salty, sour and bitter) and the umami taste, and several of these reports identified diminished threshold sensitivity for at least one taste quality. Six months to one year after RT, taste acuity recovers to its previous level in many patients, but some patients show incomplete or no recovery even several years later. Taste impairment has profound effects on patients' quality of life because is associated with weight loss through reduced appetite and altered patterns of food intake. Damage to the major salivary glands during head and neck RT leads to disturbance in taste acuity. With the implementation of new radiation techniques, such as conformal and intensity-modulated RT in head and neck irradiation, the late-radiation effects can probably be reduced, but the remaining sequelae are still bothersome to the patients.