Pathological and molecular diagnosis of bilateral inguinal lymph nodes metastases from low-grade endometrial adenocarcinoma: a case report with review of the literature.

BACKGROUND: Extra-abdominal metastases in low grade endometrial carcinoma are rare events. Inguinal lymphatic spread occurs usually in advanced disease and is associated with abdominal lymph nodes involvement. To our knowledge, isolated inguinal lymph node metastases in patients with early endometrial carcinoma have never been described thus far. CASE PRESENTATION: We present an uncommon case of inguinal lymph node metastasis in a 51-year old patient with early endometrial disease without other metastatic involvement. The metastatic loci were analyzed with the recently validated method of mitochondrial DNA sequencing to demonstrate clonality of the lesions. CONCLUSIONS: We describe the first case of inguinal metastasis from intramucous endometrial carcinoma; this case confirms the unpredictable spread of endometrial neoplasia and the importance of both patient's history and physical examination in good clinical practice.

Prognostic Impact of Pretreatment Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography SUVmax in Patients With Locally Advanced Cervical Cancer.

OBJECTIVE: The aim of this study was to investigate the impact of SUVmax fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) measured in the primary tumor, pelvic and para-aortic node with disease-free survival (DFS) and overall survival (OS) in patients with locally advanced cervical cancer. METHODS AND MATERIALS: A total of 92 patients with histological diagnosis of locally advanced cervical cancer are treated with radiochemotherapy plus brachytherapy boost from January 2008 to April 2014 in our Institution. A pretreatment FDG-PET/CT for staging and radiotherapy planning was performed, and the value of SUVmax measured in primary tumor and positive nodes was related to DFS and OS. RESULTS: Univariate analysis showed that DFS is related to FDG-PET/CT positive para-aortic nodes (P = 0.01), International Federation of Gynecology and Obstetrics (FIGO) stage of disease (P = 0.01), and primary tumor SUVmax (P = 0.02), and OS is related to positive para-aortic nodes (P = 0.01) and primary tumor SUVmax (P = 0.02).In multivariate analysis, DFS is modified by FDG-PET/CT positive para-aortic lymph nodes, stage and high T SUVmax (P = 0.02; P = 0.003; P = 0.04), but the only worse prognostic factor of OS is the high SUVmax in the primary tumor (P = 0.01). CONCLUSIONS: We found that T SUVmax, stage, and para-aortic lymph node status assessed by FDG-PET were independent prognostic factors of DFS, whereas only T SUVmax correlated with OS.

Palliative electro-chemotherapy in elderly patients with vulvar cancer: A phase II trial.

OBJECTIVE: The primary endpoint of this trial was to assess clinical response (cCR) of squamocellular vulvar cancer (V-SCC) in elderly patients treated with electro-chemotherapy (ECT). Secondary endpoints were symptoms relief and local tumor control. METHODS: A phase II study was designed and elderly patients with V-SCC unfit for other treatments were treated. Response Evaluation Criteria in Solid Tumors (RECIST criteria) were applied to evaluate tumor response. Quality of life (QoL) was evaluated by visual analogue score (VAS) for pain and four items of vulvar cancer subscale (VCS), of functional assessment of vulvar cancer therapy (FACT-V) [16], before, one month after the procedure and during follow-up. RESULTS: Median age was 85 years (range 66-96 years). One month after treatment complete response was observed in 13 patients (52%), partial response in 7 (28%), stable disease in 3 (12%), and progressive disease in 2 (8%). Local tumor control at 1 and 6 months was 91% and 53%, respectively. Symptom free survival at 1 and 6 months was 78% and 40%, respectively, with significant reduction of pain (P < 0.01). One-year overall survival was 34%. CONCLUSIONS: Our study showed that ECT produces high response rate with significant reduction of pain and improvement of local symptoms.

Electrochemotherapy can be used as palliative treatment in patients with repeated loco-regional recurrence of squamous vulvar cancer: a preliminary study.

OBJECTIVE: Electrochemotherapy (ECT) is an attractive treatment for solid cutaneous tumours with a good response rate (55-92%). No studies have evaluated ECT performed in vulvar cancer. The aim of our study was to evaluate the safety, local tumour efficacy and relief of symptoms of ECT treatment in patients affected by recurrence of squamocellular vulvar cancer (V-SCC) unsuitable for standard treatments. METHODS: We enrolled nine patients with histological diagnosis of recurrence of V-SCC. Intravenous bleomycin was injected under general sedation after an accurate mapping of all lesions and ECT was performed. Patients were reviewed after one, three and six months. Response to therapy was evaluated using RECIST criteria and quality of life (QoL) was evaluated via questionnaires. RESULTS: The median age was 84 years (range 80-90 years). The main location of recurrences was the vulva (87.5%). Multiple lesions were present in 25% of cases. No peri-operative complications were observed. Response to therapy was complete in 62.5% of patients, partial in 12.5%, no change was observed in 12.5% and progression of disease in 12.5% of patients respectively. Evaluation of symptoms showed a significant reduction of pain, bleeding, odour (p < 0.04) and urinary discomfort (p < 0.04). We observed two relapses at four and seven months after treatment. After nine months fifty percent of patients were alive. CONCLUSIONS: Our preliminary study showed that ECT is a suitable procedure in elderly patients with loco-regional vulvar cancer relapses. ECT can be used as palliative therapy and the treatment relieves symptoms and improves QoL.

Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls.

Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.

Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT).

Malignant Pleural Mesothelioma (MPM) is a rare malignancy with an overall poor prognosis. The standard therapeutic strategy in early-stage disease is trimodality therapy. In this publication, we report the preliminary toxicity results of the first 20 patients treated with accelerated hypofractionated radiotherapy. Between July 2017 to June 2019, 20 MPM patients were enrolled and treated with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. Only one case of G3 toxicity was reported, which was a bilateral pneumonitis that occurred two years after treatment probably due to superinfection. Median Time to Progression reached 18.2 months while one- and three-year Overall Survival rates were 85% (95% CI:60.4-94.9) and 49.5% (95% CI:26.5-68.9), respectively. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. Survival rates and Time to Progression are encouraging.

Locoregional treatment of de novo stage IV breast cancer in the era of modern oncology.

Approximately 6% of metastatic breast cancers arise de novo. While systemic therapy (ST) remains the treatment backbone as for patients with metachronous metastases, locoregional treatment (LRT) of the primary tumor remains a controversial method. The removal of the primary has an established role for palliative purposes, but it is unclear if it could also determine a survival benefit. Retrospective evidence and pre-clinical studies seem to support the removal of the primary as an effective approach to improve survival. On the other hand, most randomized evidence suggests avoiding LRT. Both retrospective and prospective studies suffer several limitations, ranging from selection bias and outdated ST to a small sample of patients. In this review we discuss available data and try to identify subgroups of patients which could benefit the most from LRT of the primary, to facilitate clinical practice decisions, and to hypothesize future studies design on this topic.

Oligometastatic breast cancer and metastasis-directed treatment: an aggressive multimodal approach to reach the cure.

Metastatic breast cancer (BC) is considered an incurable disease and is usually treated with palliative intent. However, about 50% of metastatic BCs present with only a few metastatic lesions and are characterized by longer overall survival. These patients, defined as oligometastatic, could benefit from a multimodal approach, which combines systemic therapy with metastasis-directed treatment (stereotactic ablative therapy or surgery). The current definition of oligometastatic seems incomplete since it is based only on imaging findings and does not include biological features, and the majority of relevant data supporting this strategy comes from retrospective or non-randomized studies. However, the chance of reaching long-term complete remission or even a cure has led to the development of randomized trials investigating the impact of combined treatment in oligometastatic BC (OMBC). The SABR-COMET trial, the first randomized study to include BC patients, showed promising results from a combination of stereotactic ablative radiotherapy and systemic therapy. Considering the randomized trial's results, multidisciplinary teams should be set up to select OMBC patients who could achieve long-term survival with aggressive multimodal treatment.

Hypofractionated volumetric modulated arc therapy (VMAT) for fragile patients with oesophageal cancer.

PURPOSE: To evaluate the feasibility, safety, and dosimetric results of volumetric modulated arc therapy (VMAT) to deliver hypofractionated radiotherapy (RT) in oesophageal cancer patients, unfit for a multimodality curative strategy. PATIENTS/METHODS: From 2010 to 2017, 22 patients were treated with hypofractionated VMAT for palliative/symptomatic setting. The prescription dose was 40 Gy in 16 fractions (EQD2 41.7 Gy considering an α/ß ratio of 10 Gy, and 44 Gy considering an α/ß ratio of 3 Gy). RESULTS: Eight patients (36%) were symptomatic for grade 3 baseline dysphagia. RT was generally well tolerated, and no patient interrupted the daily treatment. Acute toxicity was generally mild; no G3 acute toxicities were reported. At the end of treatment, 5 patients (22.7%) experienced a stable dysphagia and 14 (63.6%) an improvement of baseline dysphagia, while 3 patients (13.7%) reported a worsening of oesophagitis. At a mean follow-up of 8.7 months, 15 patients (79%) had a complete clinical recovery (G0-1) of the symptomatic moderate/severe dysphagia. At 3 months after the end of RT, seven patients (31.8%) achieved a partial or complete response. Two coplanar arcs were employed for VMAT delivery. Dosimetric results were consistent in terms of both target coverage and normal tissue sparing. Finally, 1-year progression-free and overall survival was 20% and 27.3%, respectively. CONCLUSIONS: Hypofractionated VMAT was feasible, safe, and effective to deliver symptomatic radiation in locally advanced oesophageal cancer patients, non-suitable for a standard curative treatment.

Patient-based low dose cone beam CT acquisition settings for prostate image-guided radiotherapy treatments on a Varian TrueBeam linear accelerator.

OBJECTIVE: To evaluate the performance of low dose cone beam CT (CBCT) acquisition protocols for image-guided radiotherapy of prostate cancer. METHODS: CBCT images of patients undergoing prostate cancer radiotherapy were acquired with the settings currently used in our department and two low dose settings at 50% and 63% lower exposure. Four experienced radiation oncologists and two radiation therapy technologists graded the images on five image quality characteristics. The scores were analysed through Visual Grading Regression, using the acquisition settings and the patient size as covariates. RESULTS: The low dose acquisition settings have no impact on the image quality for patients with body profile length at hip level below 100 cm. CONCLUSIONS: A reduction of about 60% of the dose is feasible for patients with size below 100 cm. The visibility of low contrast features can be compromised if using the low dose acquisition settings for patients with hip size above 100 cm. ADVANCES IN KNOWLEDGE: Low dose CBCT acquisition protocols for the pelvis, based on subjective evaluation of patient images.

The role of radiotherapy in elderly women with early-stage breast cancer treated with breast conserving surgery.

OBJECTIVE: To analyze the impact of adjuvant radiotherapy (RT) on ipsilateral breast recurrence (IBR) and overall survival (OS) in patients older than 69 years with early-stage breast cancer. METHODS: From January 2007 to June 2015, we analyzed retrospectively 137 women with estrogen receptor-positive T1-2 invasive breast cancer, with negative axillary lymph nodes, dividing them into 2 subgroups: 70 to 79 years and older than 79 years. RESULTS: After a median follow-up of 43.2 months, the 3-year IBR-free survival in patients treated with surgery plus RT was 98.8% and 92.1% in patients treated with surgery alone, with a significant difference (p = .01). Radiotherapy did not impact overall survival (p = .10). A higher percentage of patients aged between 70 and 79 years received RT after conservative surgery if compared with the older subgroup (p < .01). CONCLUSIONS: In elderly women, adjuvant RT reduced the IBR, but did not improve OS.

Concurrent chemoradiation with volumetric modulated Arc therapy of patients treated for anal cancer-acute toxicity and treatment outcome.

BACKGROUND: to report the acute toxicity and clinical results in patients with anal cancer treated with volumetric modulated arc therapy (VMAT) concomitant with chemotherapy. METHODS: A cohort of 21 patients with histologically confirmed squamous cell carcinoma of the anal canal was treated with VMAT and chemotherapy. Dose prescription was 39.6 Gy, 1.8 Gy/ fraction for the elective nodal PTV, the macroscopic (tumor and involved lymph nodes) PTV doses were 14.4 Gy up to a total dose of 54 Gy in 4 patients and 19.8 up to 59.4 Gy in 15 patients. One patient received a boost dose of 18 Gy up to a total dose of 57.6 Gy and another one was treated with 36 Gy and boost of 19.8 Gy up to a total dose of 55.8 Gy. Chemotherapy with MMC and 5-FU/Capecitabine was administered concomitantly. End points were local control (LC), disease-free survival (DFS) and overall survival (OS). RESULTS: Median follow-up time was 35.5 months. Two year OS was 91%, DFS was 73% and LRC was 81%. Acute dermatological toxicity G3 was recorded in one patient, ten patients (47.6%) experienced a G2 skin toxicity, while G1 toxicity was registered in eight patients (38%). One patient developed Grade 3 acute gastrointestinal (GI) toxicity, two patients (9.5%) experienced grade 2 acute GI toxicity and ten patients (47.6%) G1 toxicity. Acute genitourinary toxicity G1 was recorded in ten patients (47.6%). CONCLUSIONS: Our results support VMAT as standard radiotherapy technique in the treatment of patients with anal cancer.

Advanced gastric cancer: What we know and what we still have to learn.

Gastric cancer is a common neoplastic disease and, more precisely, is the third leading cause of cancer death in the world, with differences amongst geographic areas. The definition of advanced gastric cancer is still debated. Different stadiating systems lead to slightly different stadiation of the disease, thus leading to variations between the single countries in the treatment and outcomes. In the present review all the possibilities of treatment for advanced gastric cancer have been analyzed. Surgery, the cornerstone of treatment for advanced gastric cancer, is analyzed first, followed by an investigation of the different forms and drugs of chemotherapy and radiotherapy. New frontiers in treatment suggest the growing consideration for intraperitoneal administration of chemotherapeutics and combination of traditional drugs with new ones. Moreover, the necessity to prevent the relapse of the disease leads to the consideration of administering intraperitoneal chemotherapy earlier in the therapeutical algorithm.

Brachytherapy in non melanoma skin cancer of eyelid: a systematic review.

PURPOSE: Non melanoma skin cancers (NMSC) of eyelid are uncommon. Many treatments approach are available with surgery being considered as the gold standard. Radiotherapy is an effective alternative in patients unfit for surgery. Brachytherapy (BT) might be a better therapeutic option due high radiation dose concentration to the tumor and rapid dose fall-off resulting in normal tissues sparing. The aim of this review is to evaluate local control, toxicity, and functional cosmetic outcome of BT in NMSC of eyelid. MATERIAL AND METHODS: A systematic search of the bibliographic databases PubMed, Scopus, and Cochrane Library from the earliest possible date through October 2015 was performed. Only studies published in English were included. RESULTS: Six articles fulfilled the selection criteria and were included in our review. Due to high risk of bias, all studies were classified to provide a low level of evidence (according to Scottish Intercollegiate Guidelines Network Classification). No randomized controlled trials or case control studies were founded. Brachytherapy was well tolerated with acceptable toxicity and high local control rates (median: 95.2%). Functional and cosmetic outcome were reported in five study as acceptable good functional-cosmetic outcome (median: 100%). CONCLUSIONS: To date, few evidences are available on the role of BT in eyelid NMSC, and they show satisfactory results in terms of local control and functional cosmetic outcome. Therefore, prospective controlled trials are justified.

Pretherapeutic dosimetry in patients affected by metastatic thyroid cancer using 124I PET/CT sequential scans for 131I treatment planning.

PURPOSE: This study evaluates the use of sequential I PET/CT for predicting absorbed doses to metastatic lesions in patients with differentiated thyroid cancer undergoing I therapy. METHODS: From July 2011 until July 2013, 30 patients with metastatic differentiated thyroid cancer were enrolled. Each participant underwent PET/CT at 4, 24, 48, and 72 hours with 74 MBq of I. Blood samples and whole-body exposure measurements were obtained to calculate blood and red marrow doses. Activity concentrations and lesion volumes obtained from PET/CT were used to evaluate tumor doses with medical internal radiation dose formalism and spheres modeling. Mean administered I therapeutic dose was 5994 MBq (range, 1953-11,455 MBq). RESULTS: I PET/CT demonstrated all lesions detected by posttherapy I whole-body scans. Mean dose rates for blood, red marrow, and lesions were as follows: 0.07 ± 0.02 mGy/MBq, 0.05 ± 0.02 mGy/MBq, and 46.5 ± 117 mGy/MBq, respectively. Despite the high level of thyroid-stimulating hormone and CT detectable lesions, 15 of 30 patients did not show any abnormal I uptake. CONCLUSIONS: The quantitative value of I PET/CT allows simple and accurate evaluation of lesion dosimetry following medical internal radiation dose formalism. Negative I PET/CT predicts absence of iodine avidity, potentially allowing avoidance of therapeutically ineffective I administration.