Omission of postoperative radiation after breast conserving surgery: A progressive paradigm shift towards precision medicine

Radiation therapy is a standard therapeutic option in the post-operative setting for early breast cancer patients after breast conserving surgery, providing a substantial benefit in reducing the risk of local relapse with a consequent survival gain. Nevertheless, the reduction in the burden related to treatment is becoming crucial in modern oncology for both local and systemic therapies and investigational efforts are being put forward by radiations oncologists to identify a subset of women at very low risk to be potentially omitted from post-operative irradiation after breast conservation. Clinical factors, classical pathological parameters and new predictive scores derived from gene expression and next generation sequencing techniques are being integrated in the quest toward a reliable low-risk profile for breast cancer patients. We herein provide a comprehensive overview on the topic

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Breast conservation surgery (BCS) followed by radiation therapy (RT) is the local treatment of choice for an increasing percentage of women with breast cancer (BC). Surgical techniques for contemporary breast conservation are sophisticated and sensitive to aesthetic considerations

Stereotactic reirradiation for local failure of brain metastases following previous radiosurgery: Systematic review and meta-analysis

Introduction: Local failure (LF) following stereotactic radiosurgery (SRS) of brain metastases (BM) may be treated with a second course of SRS (SRS2), though this procedure may increase the risk of symptomatic radionecrosis (RN). Methods: A literature search was conducted according to PRISMA to identify studies reporting LF, overall survival (OS) and RN rates following SRS2. Meta-analysis was performed to identify predictors of RN. Results: Analysis included 11 studies (335 patients,389 metastases). Pooled 1-year LF was 24 %(CI95 % 19–30 %): heterogeneity was acceptable (I2 = 21.4 %). Median pooled OS was 14 months (Confidence Interval 95 %, CI95 % 8.8–22.0 months). Cumulative crude RN rate was 13 % (95 %CI 8 %–19 %), with acceptable heterogeneity (I2 = 40.3 %). Subgroup analysis showed higher RN incidence in studies with median patient age ≥59 years (13 % [95 %CI 8 %–19 %] vs 7 %[95 %CI 3 %–12 %], p = 0.004) and lower incidence following prior Whole Brain Radiotherapy (WBRT, 19 %[95 %CI 13 %–25 %] vs 7%[95 %CI 3 %–13 %], p = 0.004). Conclusions: SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS

Symptomatic leptomeningeal and intramedullary metastases from intracranial glioblastoma multiforme: A case report

Background. Glioblastoma multiforme infrequently metastasizes to the leptomeninges and even more rarely to the spinal cord. Moreover, very few patients with intracranial glioblastoma develop symptoms from spinal dissemination, with most patients not surviving long enough for spinal disease to become clinically evident. Case report. We present a rare case of symptomatic diffuse spinal leptomeningeal metastases simultaneously to an intramedullary lesion from an intracranial glioblastoma multiforme. After the diagnosis of spinal metastases the patient was treated with limited-field spinal radiotherapy (30 Gy in 3-Gy fractions). Results. Radiotherapy on the main spinal lesions provided either relief from pain or mild improvement of neurological deficits. The patient died due to intracranial progression 4 months after diagnosis of spinal seeding and 17 months after diagnosis of the primary disease. We analyzed leptomeningeal and spinal metastases from glioblastoma multiforme with reference to the literature. Conclusions. Radiotherapy for spinal disease may provide important symptom relief but the prognosis of these patients remains dramatically poor. As the local control of primary glioblastoma multiforme has improved with recent therapeutic advances, distant metastasis from high-grade gliomas is likely to become a more common clinical problem and such patients need to be included in clinical trials to evaluate new therapeutic approaches

Dyspnea in Patients Receiving Radical Radiotherapy for Non-Small Cell Lung Cancer: A Prospective Study

Background and Purpose: Dyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry. Material and Methods: Eighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters. Results: The median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V30 p=0.017; V40 p=0.026; V50 p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V30 p=0.05; V40 p=0.026; V50 p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V40; p=0.041, V50; p=0.037) and dyspnea VAS score at 6 months (V40; p=0.027) post-treatment. Conclusions: Worsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjectiv

Loco-regional adjuvant radiation therapy in breast cancer patients with positive axillary lymph-nodes at diagnosis (CN2) undergoing preoperative chemotherapy and with complete pathological lymph-nodes response. Development of GRADE (Grades of recommendation, assessment, Development and Evaluation) recommendation by the Italian Association of radiation therapy and Clinical Oncology (AIRO)

Objective: To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST). Material and Methods: Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events. Results: Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63\u20131.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events. Conclusions: Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy

Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients

BACKGROUND: Proton-pump-inhibitors (PPIs) are frequently prescribed for the management of anticancer drug-related gastrointestinal symptoms. Palbociclib is a weak base with pH-dependent solubility and potential drug-drug interaction at the absorption level may affect clinical pharmacokinetics. The current study was aimed at investigating the effect of co-administration of PPIs and palbociclib on progression-free survival (PFS) in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: Patients affected by estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, who were candidates for first-line treatment with palbociclib, were enrolled in this retrospective observational study. Patients were defined as ‘no concomitant PPIs’ if no PPIs were administered during palbociclib treatment, and as ‘concomitant PPIs’ if the administration of PPIs covered the entire or not less than two-thirds of treatment with palbociclib. All clinical interventions were made according to clinical practice. RESULTS: A total of 112 patients were enrolled in the study; 56 belonged to the ‘no concomitant PPIs’ group and 56 to the ‘concomitant PPIs’ group. Seventy-one patients were endocrine-sensitive and received palbociclib and letrozole, and 43 were endocrine-resistant and were treated with palbociclib and fulvestrant. The most prescribed PPI was lansoprazole. Patients taking PPIs had a shorter PFS than those taking palbociclib and endocrine therapy alone (14.0 versus 37.9 months, P 2 hematological toxicities [Common Terminology Criteria for Adverse Events (CTCAE) scale]. CONCLUSIONS: The present study demonstrates that concomitant use of PPIs in mBC patients treated with palbociclib has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPIs with caution in these patients, strictly adhering to the indications in the summary of product characteristics (RCP)