Lorenzo Falcinelli

Outcome of a phase II prospective study on partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy

BACKGROUND AND PURPOSE Partial breast irradiation (PBI) is an alternative to whole-breast irradiation after breast-conserving surgery in selected patients. Until the results of randomized phase III studies are available, phase II studies inform about PBI. We report the 5 year results of a phase II prospective study with PBI using interstitial multi-catheter high-dose-rate brachytherapy (ClinicalTrials.gov Identifier: NCT00499057). METHODS Hundred patients received PBI (4 Gy, twice a day for 4 days, until 32 Gy). Inclusion criteria were: age ≥ 40years, infiltrating carcinoma without lobular histology, ductal in situ carcinoma, tumor size ≤ 2.5 cm, negative surgical margins and axillary lymph nodes. RESULTS At a median follow-up of 60 months late toxicity occurred in 25 patients; the 5-year probability of freedom from late toxicity was 72.6% (95% CI: 63.7-81.7). Tamoxifen was the only significant risk factor for late toxicity. Cosmetic results, judged by physicians and patients, were good/excellent in 98 patients. Three local relapses (1 true, 2 elsewhere) and 1 regional relapse occurred. The 5-year probability of local or regional relapse-free survival was 97.7% (95% CI: 91.1-99.4) and 99.0% (95% CI: 92.9-99.8), respectively. CONCLUSION PBI with interstitial multi-catheter brachytherapy is associated with low relapse and late toxicity rates.

PET and PET–CT in radiation treatment planning for lung cancer

This review analyzes PET images in radiotherapy treatment planning for lung cancer patients and discusses the most controversial current issues. Computed tomography images are commonly used to assess location and extension of target volumes and organs at risk in radiotherapy treatment planning. Although PET is more sensitive and specific, contouring on PET images is difficult because tumor margins are indistinct, due to heterogeneous 18fluorodeoxyglucose uptake distribution and limited spatial resolution. The best target delineation criteria have not yet been established. In non-small-cell lung cancer, PET appears to improve sparing of organs at risk and reduce the risk of toxicity; prescribed doses can be increased. Data are scarce on small-cell lung cancer.

Survival outcomes and incidence of brain recurrence in high-grade neuroendocrine carcinomas of the lung: Implications for clinical practice.

BACKGROUND Among patients with advanced high-grade neuroendocrine carcinoma (HGNEC) of the lung, the optimal therapeutic management is much less established for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung cancers (SCLCs). We evaluated the survival outcomes and incidence of brain recurrence of advanced LCNECs, and compared them with those of a population of SCLCs matched by stage. MATERIALS AND METHODS Forty-eight unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis. The efficacy of platinum-etoposide chemotherapy with or without thoracic radiotherapy (TRT) and/or prophylactic cranial irradiation (PCI) was investigated. RESULTS Overall response was significantly lower for LCNECs compared with SCLCs for both stage III (43.8% vs 90.6% respectively, P=0.004) and stage IV (43.3% vs 64.5%, respectively, P=0.04). Similarly, an inferior outcome was observed in terms of progression-free survival (PFS), and overall survival (OS) for LCNECs compared with SCLCs, which, however, reached significance only for stage III disease (median: 5.6 vs 8.9 months, P=0.06 and 10.4 vs 17.6 months, P=0.03 for PFS and OS, respectively). In the lack of PCI, LCNECs showed a high cumulative incidence of brain metastases, as 58% and 48% of still living stage III and IV patients, respectively, developed brain metastases at 18 months. CONCLUSION Patients with advanced LCNECs are at high risk for brain recurrence. Unresected stage III LCNECs treated with platinum-etoposide with or without TRT bear a dismal prognosis, when compared indirectly with SCLC counterparts. Randomized trials should evaluate whether PCI could improve survival of advanced LCNECs.

Bronchiolitis obliterans organizing pneumonia after radiation therapy for lung cancer: a case report

Bronchiolitis obliterans organizing pneumonia (BOOP), also known as cryptogenic organizing pneumonia, has mainly been described in patients with breast cancer who received radiotherapy after breast-conserving surgery. In this rare case, a 70-year-old man with left apical squamous lung cancer developed BOOP after radiotherapy and only one cycle of concomitant chemotherapy.This case report draws attention to the development of this syndrome in the unusual setting of lung cancer, advising prompt steroid treatment when diagnostic images reveal the characteristic signs of the disease.

Helical tomotherapy for duodenal adenocarcinoma in an elderly patient: A case report

To evaluate the efficacy and feasibility of external beam radiotherapy (EBRT) for duodenal adenocarcinoma in an 84-year-old female who underwent EBRT (2.2 Gy/d for a total dose of 46.2 Gy) using helical tomotherapy (HT). Toxicity was evaluated on the National Cancer Institute’s common toxicity criteria (CTCAE 3.0). The patient completed the treatment without G3-G4 toxicity. After 22-mo follow-up, she is alive and well, in complete remission with no late side effects. HT seems to be feasible and effective for duodenal adenocarcinoma in old to very old patients.

Treatment outcomes and patterns of radiologic appearance after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) for lung tumours

OBJECTIVE To evaluate treatment outcomes and patterns of CT lung injury after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) in a series of inoperable lung lesions. METHODS 68 patients who were medically inoperable (69 lesions) without evidence of viable extrathoracic disease were included. Dose prescription was driven by tumour location (hilar/pericentral vs peripheral) and/or target volume. 52% of the lesions received a biological equivalent dose (BED10) ≥100 Gy. Assessment of tumour response was based on the Response Evaluation Criteria in Solid Tumours 1.1 criteria coupled with fluorine-18 fludeoxyglucose/positron emission tomography-CT. Toxicity monitoring was focused on treatment-related pulmonary adverse events according to the Common Terminology Criteria for Adverse Events v. 4.0. Acute and late events were classified as radiation pneumonitis (RP) and radiation fibrosis (RF), respectively. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of survival were performed using the Cox proportional hazards model. RESULTS After a median follow-up of 12 months (range, 3-31 months), no instances of ≥Grade 4 RP was documented, and clinically severe (Grade 3) RP occurred in 5.8% of the patients. 2 (3%) patients developed a late severe (≥Grade 3) symptomatic RF. No specific pattern of CT lung injury was demonstrated, in both acute and late settings. Median overall survival (OS) and progression-free survival (PFS) for the entire population were 30.8 and 14.1 months, respectively. At multivariate analysis (MVA), BED10 ≥ 100 Gy and KPS ≥ 90 emerged as significant prognostic factors for OS (p = 0.01 and p = 0.001, respectively), and BED10 ≥ 100 Gy for PFS (p = 0.02). CONCLUSION Our findings show that HHT adjusted for tumour location and/or target volume is an effective treatment with an acceptable toxicity profile in patients who are medically inoperable with lung tumours and is not associated with a specific pattern of lung injury. Therefore, it can represent a viable option when conventional stereotactic ablative radiotherapy facilities are not available. Advances in knowledge: The present study is among the largest series addressing the role of HHT for inoperable lung tumours. This technique is safe and effective and is not associated with a specific pattern of lung injury, at least at early and average time points.

Comparison of Helical Tomotherapy and Direct Tomotherapy in Bilateral Whole Breast Irradiation in a Case of Bilateral Synchronous Grade 1 and Stage 1 Breast Cancer

Patient: Female, 60 Final Diagnosis: Complete remission Symptoms: None Medication: — Clinical Procedure: Radiotherapy Specialty: Oncology Objective: Rare disease Background: Synchronous bilateral breast cancer is rare. A case is presented where whole breast irradiation (WBI) was planned after breast conserving surgery in a patient with synchronous bilateral breast cancer. A comparison was made between the feasibility of helical tomotherapy and direct tomotherapy. Case Report: A 60-year-old woman was found to have bilateral breast nodules on routine mammographic screening, resulting in bilateral lumpectomy and sentinel lymph node biopsy. Histopathology showed a 6 mm diameter invasive ductal carcinoma in the right breast (Grade 1, hormone receptor positive, HER2 negative) and an 8mm diameter tubular carcinoma in the left breast (Grade 1, hormone receptor positive, HER2 negative). Lymph node biopsy and histology, chest X-ray, abdominal ultrasound scan, and bone scintigraphy were negative for metastases (both tumors were Stage 1). Adjuvant therapy with commenced with anastrozole, but no chemotherapy was given. Clinical target volumes (CTVs) were contoured on computed tomography (CT) images. For planning target volumes (PTVs), CTVs were expanded by 1 cm in all directions, except for the medial 5 mm. Since dose constraints to organs at risk (OARs) were beyond established limits, CTVs were expanded by 5 mm. For PTVs, OAR doses and homogeneity indices for helical tomotherapy and direct tomotherapy were compared. Helical tomotherapy provided better target volume coverage and OAR sparing than direct tomotherapy. Conclusions: In a case of bilateral synchronous Stage 1 and Grade 1 breast cancer, helical tomotherapy appeared more suitable than direct tomotherapy.

Sacrum colon-rectal cancer metastasis: microwave ablation for palliative pain treatment

Local treatment of bone metastasis (BM) remains controversial in colon-rectum carcinoma for pain control. A patient developed a sacrum BM 4years after a left colectomy for an adenocarcinoma. Metastasis was treated in one session of CT-guided microwave ablation showing good pain control immediately after and on follow-up at four months.

Short-course radiotherapy with delayed surgery in unfit locally advanced rectal cancer patients.

Dear Editor: It is well known that preoperative radiotherapy (RT), alone or in combination with chemotherapy (CRT), is the standard of care for patients with locally advanced rectal cancer with both schedules being equivalent in terms of local recurrence and survival. Short-course radiotherapy (SCRT), according to a hypofractionated schedule (25 Gy in 5 fractions), followed by immediate surgery, is extensively used in resectable disease, as it offers the advantages of shorter treatment time, lower costs, and less acute toxicity. On the other hand, it is not recommended when disease down-sizing/down-staging and sphincter saving procedure are required because the interval between the end of RT and surgery is too short for rectal cancer clearance [1]. Changes in intervals between SCRT and surgery were explored both in resectable and unresectable disease. Its feasibility and effectiveness in terms of toxicity and disease downstaging, was demonstrated [2–5], even if short-term survival outcome remains unchanged [5]. From June 2007 to December 2012, 56 locally advanced rectal cancer patients (median age 79 years) who were unfit for chemotherapy due to co-morbidities (median Charlson score 7; range 5–11) and poor Karnofsky Performance Status (KPS) (23 % of cases) underwent SCRT and delayed surgery. The majority of patients (89 %) had tumors in the lower rectum; most were T3 (98 %) and nodes were diseased (N+) in 37 (66 %) patients. 25Gy in 5 fractions, in 5–7 days, were delivered to the primary tumor, and the corresponding mesorectum, with the pathological lymph nodes, plus a 2-cm cranio-caudal margin. Generally, the upper limit of target volume was below S1-S2. RTwas completed in all cases, and no patient developed severe acute toxicity. At a median time of 9 weeks from the end of RT, 46/56 patients (82 %) underwent surgical resection (anterior resection in 72 % and abdominoperineal resection in 28 % of cases); four patients (7 %) refused surgery, and six (11 %) were ineligible because of KPS deterioration. There were no surgery-related deaths. Major pathological response (tumor regression grade—TRG—1–2 according to Mandard score) was observed in 21/46 patients (45 %), with seven (15 %) obtaining pathological complete response (pCR or TRG 1 according to Mandard score). Tumor stage, tumor and node categories, were significantly down-staged compared with the initial radiological assessment, as 88 % of patients did not show node involvement. Our results compared favorable with those published in the literature, both in terms of downstaging and pCR rate [2–5]. In particular, in cohorts with both resectable and unresectable disease, about 70% of patients did not show node involvement, and pCR rates ranged from 8 to 13 % [2–5]. These studies demonstrated that a long interval between SCRT and surgery was a valid alternative to longcourse pre-operative CRT in elderly patients with poor performance status and/or co-morbidities and renewed interest in this approach for younger patients with less advanced disease who are usually treated with concomitant CRT [4, 5]. In our experience, local recurrence (LR) developed in three of the 46 surgical patients (6.5 %) and distant metastases (DM) in eight of all 56 enrolled patients (14 %). These findings compared favorable with those published in the literature [3, 5], even if a wider range of events may occur (LR 0–7 %; DM 2.8–24 %). Surgery and pathological stage adjusted for age, grade, and TRG were significant prognostic factors. In particular, surgery significantly influenced cancer-specific survival (65 vs 47 months) and distant metastases-free * Marco Lupattelli kiralupis@libero.it

Does ultrasound provide any added value in breast contouring for radiotherapy after conserving surgery for cancer

BackgroundWhole breast irradiation after conserving surgery for breast cancer requires precise definition of the target volume. The standard approach uses computed tomography (CT) images. However, since fatty breast and non-breast tissues have similar electronic densities, difficulties in differentiating between them hamper breast volume delineation. To overcome this limitation the breast contour is defined by palpation and then radio-opaque wire is put around it before the CT scan. To optimize assessment of breast margins in the cranial, caudal, medial, lateral and posterior directions, the present study evaluated palpation and CT and determined whether ultrasound (US) provided any added value.MethodsTwenty consecutive patients were enrolled after they had provided informed consent to participating in this prospective study which was approved by the Regional Public Health Ethics Committee. Palpation and US defined breast margins and each contour was marked and outlined with a fine plastic wire. Breasts were then contoured on axial CT images using the breast window width (WW) and window level (WL) (401 and 750 Hounsfield Units –HU- respectively), at which setting the plastic wires were invisible. Then, the lung window function (WW 1601 HU; WL −300 HU) was inserted to visualize the plastic wires which were used as guidelines to contour the palpable and US breast volumes. As each wire had a different diameter, both volumes were easily defined on CT slices. Results were analyzed using descriptive statistics, percentage overlap and reproducibility measures (agreement and reliability).ResultsVolumes: US gave the largest and palpation the smallest. Agreement was best between palpation and CT. Reliability was almost perfect in all correlations. Extensions: Cranial and posterior were highest with US and smallest with palpation. Agreement was best between palpation and CT in all extensions except the cranial. Since strong to almost perfect agreement emerged for all comparisons, reliability was high.ConclusionsUS may be useful in defining the cranial and posterior extensions, mainly when tumours are localized there. This study demonstrates that the now standard radio-opaque wires around the palpable breast may not be needed in breast contouring.