Francesca Arcadipane

Intensity-Modulated Radiation Therapy with Simultaneous Integrated Boost Combined with Concurrent Chemotherapy for the Treatment of Anal Cancer Patients: 4-Year Results of a Consecutive Case Series

ABSTRACT Purpose: To report the 4-year outcomes of a consecutive series of anal cancer patients treated with concurrent chemo-radiation delivered with intensity-modulated radiotherapy (IMRT), employing a simultaneous integrated boost (SIB) approach. Methods: A consecutive series of 54 patients was enrolled between 2007 and 2013. Treatment schedule consisted of 50.4 Gy/28 fractions (1.8 Gy daily) to the gross tumor volume, while the elective nodal volumes were prescribed 42 Gy/28 fractions (1.5 Gy/daily) for patients having a cT2N0 disease. Patients with cT3-T4/N0-N3 tumors were prescribed 54 (T3) or 60 (T4) Gy/30 fractions (1.8–2 Gy daily) to the gross tumor volume; gross nodal volumes were prescribed 50.4 Gy/30 fr (1.68 Gy daily) if sized ≤ 3 cm or 54 Gy/30 fr (1.8 Gy daily) if > 3 cm; elective nodal regions were given 45 Gy/30 fractions (1.5 Gy daily). Chemotherapy was administered concurrently according to the Nigros regimen. Primary endpoint was colostomy-free survival (CFS). Secondary endpoints were local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and toxicity profile. Results: Median follow up was 32.6 months (range 12–84). The actuarial probability of being alive at 4 years without a colostomy (CFS) was 68.9% (95% CI: 50.3%–84.7%). Actuarial 4-year OS, CSS, DFS, and LC were 77.7% (95% CI: 60.7–88.1%), 81.5% (95% CI: 64%–91%), 65.5% (95% CI: 47.7%–78.5%), and 84.6% (95% CI: 71.6%–92%). Actuarial 4-year metastasis-free survival was 74.4% (95% CI: 55.5%–86.2%). Maximum detected acute toxicities were as follows: dermatologic –G3: 13%; GI-G3: 8%; GU-G3: 2%; anemia-G3: 2%; neutropenia-G3:11%; G4: 2%; thrombocytopenia- G3:2%. Four-year G2 chronic toxicity rates were 2.5% (95% CI: 3.6–16.4) for GU, 14.4% (95% CI: 7.1–28) for GI, 3.9% (95% CI: 1%–14.5%) for skin, and 4.2% (95% CI: 1.1–15.9) for genitalia. Conclusions: Our study shows the feasibility of IMRT in the combined modality treatment of anal cancer, with comparable results to the literature with respect to LC, sphincter preservation and survival. Acute toxicity is lower if compared to series employing standard techniques. Our results support the use of IMRT on a routine basis for the treatment of anal cancer.

Volumetric modulated arc therapy (VMAT) in the combined modality treatment of anal cancer patients

OBJECTIVE To report clinical and dosimetric outcomes of a consecutive series of patients with anal cancer treated with volumetric-modulated arc therapy (VMAT) concomitant to chemotherapy (CT). METHODS A cohort of 39 patients underwent VMAT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumour volume (GTV) and 42 Gy/28 fractions to the elective nodal volumes for patients with cT2N0 disease. Patients with cT3-T4/N0-N3 tumours were prescribed 54 Gy/30 fractions to the GTV and 50.4 Gy/30 fractions to the gross nodal volumes if sized ≤3 cm or 54 Gy/30 fractions if > 3 cm. Elective nodal regions were given 45 Gy/30 fractions. CT was administered concurrently following Nigros regimen. The primary end point was acute toxicity. Secondary end points were colostomy-free survival (CFS), disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Dosimetric data are also provided. RESULTS Median follow-up was 21 months. Maximum acute toxicities were: dermatologic-G3: 18%; gastrointestinal-G3: 5%; genitourinary-G3: 2%; anaemia-G2: 7%; leukopenia-G3: 28%; G4: 8%; neutropenia-G3: 13%; G4: 18%; thrombocytopenia-G3: 11%; and G4: 2%. The actuarial 2-year CFS was 77.9% [95% confidence interval (CI): 54-90.4%]. Actuarial 2-year OS and CSS were 85.2% (95% CI: 60.1-95.1%), while DFS was 75.1% (95% CI: 52.4.7-88.1%). CONCLUSION Our clinical results support the use of VMAT as a safe and effective intensity-modulated radiotherapy (IMRT) option in the combined modality treatment of anal cancer, with consistent dosimetry, mild toxicity and promising sphincter preservation and survival rates. ADVANCES IN KNOWLEDGE IMRT is a standard of care for patients with anal cancer, and VMAT is a robust technical solution in this setting.

Hematologic toxicity in anal cancer patients during combined chemo-radiation: a radiation oncologist perspective

ABSTRACT Introduction: Hematologic toxicity is an important side effect occurring in patients affected with anal cancer, undergoing combined radio-chemotherapy, with consistent clinical meaningfulness. Areas covered: Since more than a half of bone marrow is comprised within the pelvic region, the radiation dose received by this functional compartment is crucial. Modern imaging modalities may provide a useful tool to identify bone marrow and new delivery technology may enhance the radiation oncologist’s possibility to selectively spare these structures, potentially decreasing acute hematologic toxicity profile in this setting. Expert commentary: Correlation between dose to pelvic structures and acute hematologic toxicity has been studied in several oncological settings, mainly on a retrospective frame. Different dose metrics were found to be correlated including mean doses and different points within the dose–volume histogram ranging from low to medium-high doses. Several imaging modalities were used to identify bone marrow both morphological and functional. Several clinical endpoints were used. In general, accounting for bone marrow during the treatment planning process may be important to decrease the acute hematologic toxicity profile during concurrent chemo-radiation in anal cancer patients. The most appropriate strategy to address this issue need further investigation and deserve validation in a prospective clinical framework.

Three-Dimensional Ultrasound-Based Image-Guided Hypofractionated Radiotherapy for Intermediate-Risk Prostate Cancer: Results of a Consecutive Case Series

External beam radiotherapy (EBRT) is a standard of care in the treatment of prostate cancer. Hypofractionation is a valid option either radiobiologically and logistically in this context. Image-guidance procedures are strongly needed to provide ballistic precision to radiation delivery. The Clarity platform allows for the acquisition of three-dimensional ultrasound scans (3D-US) to perform image-guided radiotherapy. We treated a consecutive series of intermediate-risk prostate cancer patients (according to NCCN stratification) with a hypofractionated schedule (70.2 Gy/26 fractions at 2.7 Gy/daily to the prostate gland excluding the seminal vesicles at 62.1 Gy) under 3D-US guidance with the Clarity platform. The 3-year biochemical-relapse-free survival, distant-metastases-free, cancer-specific and overall survival were 98.6% (CI: 91.1–99.6%), 98.6% (CI: 91.1–99.6%), 97.5% (CI: 94.5–99.1%), and 94.3% (CI: 90.4–96.7%), respectively. Maximum detected acute GU toxicity was G0 in 22 patients (29.7%), G1 in 30 (22.7%), G2 in 19 (25.6%), G3 in 3 (4%). Maximum detected acute GI toxicity at the end of EBRT was G0 in 42 patients (56.8%), G1 in 22 (29.7%), G2 in 9 (12.1%), G3 in 1 (1.4%). The 3-year actuarial rates of ≥ G2 late toxicities were 6.1% for genito-urinary and 8.9% for gastrointestinal. The whole image-guidance workflow resulted in being robust and reliable. EBRT delivered employing a hypofractionated schedule under 3D-US-based image guidance proved to be a safe and effective treatment approach with consistent biochemical control and a mild toxicity profile. Hence, it has been transferred into daily clinical practice in our Department.

Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer

To report on clinical outcomes of simultaneous integrated boost intensity‐modulated radiation therapy (IMRT) and concurrent chemotherapy as per Radiation Therapy Oncology Group (RTOG) 0529 protocol in anal cancer patients.

Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer

Oral mucositis (OM) is a common acute side effect during radiotherapy treatments for head and neck cancer (HNC), with a potential impact on patient’s compliance to therapy, quality of life (QoL) and clinical outcomes. Its timely and appropriate management is of paramount importance. Several quantitative scoring scales are available to properly assess OM and its influence on patient-reported outcomes (PROs) and QoL. We prospectively assessed OM in a cohort of HNC patients submitted to radiation using the Oral Mucositis Assessment Scale (OMAS), while its impact on PROs and QoL was evaluated employing the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN) and the Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-HN). Evaluation of OMAS scores highlighted a progressive increase in OM during treatment and a partial recovery after the end of radiation. These trends were correlated to PROs and QoL as evaluated with OMWQ-HN and FACT-HN questionnaires. In the present study, we provided a quantitative assessment of OM, PROs and QoL in HNC patient undergoing radiotherapy, potentially useful for future comparison.

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.

Pre-operative treatments for adenocarcinoma of the lower oesophagus and gastro-oesophageal junction: a review of the current evidence from randomized trials

Adenocarcinomas of the lower oesophagus and gastro-oesophageal junction are a complex clinico-pathological setting. Multimodality therapy is considered mandatory in most disease presentations. Nevertheless, the most appropriate treatment package has yet to be established. We herein summarize the evidence derived from randomized phase III trials on pre-operative treatments in this oncological scenario.

Risk stratification system and pattern of relapse in patients treated with adjuvant radiotherapy after radical prostatectomy.

Purpose To retrospectively evaluate the role of adjuvant radiotherapy (ART) as monotherapy in a cohort of prostate cancer patients with undetectable prostate-specific antigen (PSA) after surgery and to propose a risk stratification system. Methods Between 2003 and 2010, 174 consecutive patients were treated with ART (median dose 71 Gy) at a single institution. Subsequently, we assigned a score of 1 to the following risk factors (RF): T stage ≥3b, presurgical PSA ≥10 ng/mL, pathologic Gleason score (GS) ≥4 + 3, and positive surgical margin (R1). The scores were then summed to stratify the population into low risk (LR), intermediate risk (IR), and high risk (HR). Results Median follow-up was 61 months (range 4-105). Five-year biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and overall survival (OS) were respectively 93%, 97.1%, and 98.6%. On univariate analyses, GS was the only variable related to bRFS (p = 0.04) and to cRFS (p = 0.05). Any variable was related to OS. Kaplan-Meier analysis showed that HR patients (3-4 RF) had a worse bRFS (p = 0.02) compared to LR patients (0 RF or R1 as single RF); IR patients (1-2 RF) had a lower bRFS compared to LR patients (p = 0.06). Patients with R1 as single RF have the same bRFS as patients with 0 RF (p = 0.6) and are considered as LR patients. Conclusions Adjuvant radiotherapy leads to excellent bRFS and cRFS rates at 5 years (93.3% and 97.1%, respectively) in our population. Patients with multiple RF are at higher risk of bRFS. Patients with R1 as single RF have bRFS rates comparable to patients without any RF.

Dose to Pelvic Bone Marrow Defined with FDG-PET Predicts for Hematologic Nadirs in Anal Cancer Patients Treated with Concurrent Chemo-radiation

Abstract Purpose: To investigate whether irradiated volume of pelvic active bone marrow (ACTBM) may predict decreased blood cells nadirs in anal cancer patients undergoing concurrent chemo-radiation. Methods: Forty-four patients were analyzed and pelvic active bone marrow (ACTBM) was characterized employing 18FDG-PET. Dosimetric parameters on dose–volume histograms were correlated to nadirs with generalized linear modeling. Results: ACTBM mean dose was significantly correlated to white blood cell (β = −1.338; 95%CI: −2.455/−0.221; p = 0.020), absolute neutrophil count (β = −1.651; 95%CI: −3.284/−0.183; p = 0.048), and platelets (β = −0.031; 95%CI: −0.057/−0.004; p = 0.024) nadirs. Other dosimetric parameters were found to be correlated (ACTBM-V10,-V20,-V30and-V40). Conclusions: 18FDG-PET is able to define active bone marrow and may predict for decreased blood cells count nadirs.