V. Picardi

Volumetric Modulated Arc Therapy with Simultaneous Integrated Boost for Locally Advanced Rectal Cancer

AIMS To report the feasibility of volumetric modulated arc therapy (VMAT) for neoadjuvant radiotherapy in locally advanced rectal cancer in a dose-escalation protocol and simultaneous integrated boost (SIB) approach. Moreover, the VMAT technique was compared with three-dimensional conformal radiotherapy (3D-CRT) and fixed-field intensity modulated radiotherapy (IMRT), in terms of target coverage and irradiation of organs at risk. MATERIALS AND METHODS Eight patients with locally advanced rectal cancer were treated with the SIB-VMAT technique. The VMAT plans were compared with 3D-CRT and IMRT techniques in terms of several clinically dosimetric parameters. The number of monitor units and the delivery time were analysed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a two-dimensional array of ionisation chambers. RESULTS All techniques meet the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformality. VMAT is associated with 40, 53 and 58% reduction in the percentage of volume of small bowel irradiated to 30, 40 and 50Gy, compared with 3D-CRT. No significant differences were found with respect to SIB-IMRT. VMAT plans showed a significant reduction of monitor units by nearly 20% with respect to IMRT and reduced treatment time from 14 to 5min for a single fraction. CONCLUSIONS SIB-VMAT plans can be planned and carried out with high quality and efficiency for rectal cancer, providing similar sparing of organs at risk to SIB-IMRT and resulting in the most efficient treatment option. SIB-VMAT is currently our standard approach for radiotherapy of locally advanced rectal cancer.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: Results of a phase II study

Abstract Background. An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. Material and methods: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehans design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. Results: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12–55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18–63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1–2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. Conclusion. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer

BackgroundRadiotherapy (RT) is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV) in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI) in the preoperative and definitive treatment of pancreatic cancer.MethodsThe anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries.ResultsWe proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided.ConclusionsThe proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

Late tonsil metastases from renal cell cancer: a case report.

The occurrence of renal carcinoma metastasis to the head and neck region is extremely rare. Some authors have reported metastasis of renal cell carcinoma to the parotid glands, nose and paranasal sinus, tongue, larynx, thyroid and palatine tonsil. In this report we describe a rare case of renal cell cancer metastasized to the right tonsil in a 76-year-old man with previously diagnosed bone and lung metastases. To the best of our knowledge this is the first documented example of radiotherapy treatment in this type of presentation. Radiotherapy was effective in treating the lesion with satisfactory functional results.

Quality of Life and Toxicity of Stereotactic Radiotherapy in Pancreatic Tumors: A Case Series

Aim: To analyze the results of extracranial stereotactic radiotherapy (ESRT) experience in pancreatic cancer patients. Methods: Four noncoplanar fixed beams were used in all patients. Results: Analysis of 16 patients was carried out. Overall response rate was 56.2%. Fifteen patients experienced local and/or distant progression of disease (median follow-up: 24 months). Two-year local progression-free, distant progression-free, and overall survivals were 85.7%, 58.7%, and 50.0%, respectively. Toxicity was less than grade 2 in all, although 1 patient had severe duodenal bleeding. Quality of life scores were unchanged. Conclusions: ESRT was associated with low complication rate, and not worsening the patients’ quality of life.

Feasibility Study of Moderately Accelerated Intensity-Modulated Radiotherapy Plus Concurrent Weekly Cisplatin After Induction Chemotherapy in Locally Advanced Head-and Neck Cancer

PURPOSE To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). METHODS AND MATERIALS Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m(2) plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. RESULTS In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. CONCLUSIONS In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

3D-Conformal Versus Intensity-Modulated Postoperative Radiotherapy of Vaginal Vault: A Dosimetric Comparison

We evaluated a step-and-shoot IMRT plan in the postoperative irradiation of the vaginal vault compared with equispaced beam arrangements (3-5) 3D-radiotherapy (RT) optimized plans. Twelve patients were included in this analysis. Four plans for each patient were compared in terms of dose-volume histograms, homogeneity index (HI), and conformity index (CI): (1) 3 equispaced beam arrangement 3D-RT; (2) 4 equispaced beam arrangement 3D-RT; (3) 5 equispaced beam arrangement 3D-RT; (4) step-and-shoot IMRT technique. CI showed a good discrimination between the four plans. The mean scores of CI were 0.58 (range: 0.38-0.67) for the 3F-CRT plan, 0.58 (range: 0.41-0.66) for 4F-CRT, 0.62 (range: 0.43-0.68) for 5F-CRT and 0.69 (range: 0.58-0.78) for the IMRT plan. A significant improvement of the conformity was reached by the IMRT plan (p < 0.001 for all comparisons). As expected, the increment of 3D-CRT fields was associated with an improvement of target dose conformity and homogeneity; on the contrary, in the IMRT plans, a better conformity was associated to a worse target dose homogeneity. A significant reduction in terms of D(mean), V90%, V95%, V100% was recorded for rectal and bladder irradiation with the IMRT plan. Surprisingly, IMRT supplied a significant dose reduction also for rectum and bladder V30% and V50%. A significant dosimetric advantage of IMRT over 3D-RT in the adjuvant treatment of vaginal vault alone in terms of treatment conformity and rectum and bladder sparing is shown.

Neoadjuvant Accelerated Concomitant Boost Radiotherapy and Multidrug Chemotherapy in Locally Advanced Rectal Cancer: A Dose-Escalation Study

ObjectivesTo determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients. MethodsPatients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria. ResultsForty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level. ConclusionsAn intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.

Postoperative intensity-modulated radiotherapy in low-risk endometrial cancers: final results of a phase i study.

PURPOSE To determine the maximum tolerated dose of short-course radiotherapy (intensity-modulated radiotherapy technique) to the upper two thirds of the vagina in endometrial cancers with low risk of local recurrence. PATIENTS AND METHODS A Phase I clinical trial was performed. Eligible patients had low-risk resected primary endometrial adenocarcinomas. Radiotherapy was delivered in 5 fractions over 1 week. The planning target volume was the clinical target volume plus 5 mm. The clinical target volume was defined as the upper two thirds of the vagina as evidenced at CT simulation by a vaginal radio-opaque device. The planning target volume was irradiated by a seven-field intensity-modulated radiotherapy technique, planned by the Plato Sunrise inverse planning system. A first cohort of 6 patients received 25 Gy (5-Gy fractions), and a subsequent cohort received 30 Gy (6-Gy fractions). The Common Toxicity Criteria scale, version 3.0, was used to score toxicity. RESULTS Twelve patients with endometrial cancer were enrolled. Median age was 58 years (range, 49-74 years). Pathologic stage was IB (83.3%) and IC (16.7%). Median tumor size was 30 mm (range, 15-50 mm). All patients completed the prescribed radiotherapy. No patient experienced a dose-limiting toxicity at the first level, and the radiotherapy dose was escalated from 25 to 30 Gy. No patients at the second dose level experienced dose-limiting toxicity. The most common Grade 2 toxicity was gastrointestinal, which was tolerable and manageable. CONCLUSIONS The maximum tolerated dose of short-course radiotherapy was 30 Gy at 6 Gy per fraction. On the basis of this result, we are conducting a Phase II study with radiotherapy delivered at 30 Gy.

FOLFIRI-bevacizumab and concurrent low-dose radiotherapy in metastatic colorectal cancer: preliminary results of a phase I–II study

Abstract Background: To evaluate the effectiveness of low-dose radiation therapy (LDRT) and FOLFIRI-bevacizumab (FOLFIRI-B) combination in metastatic colorectal cancer. Methods: The primary objective of the study is to raise the clinical complete response (CR) rate from 5% to 25%. Secondary objectives include toxicity and progression-free survival. Patients underwent 12 FOLFIRI-B cycles plus two daily LDRT (20 cGy/6-hour interval) on the first and second days of each cycle. Results: CR and toxicity of 10 patients are reported. Considering irradiated sites, 10/10 patients had clinical partial response (PR) (7/10) or CR (3/10). Three clinical PR patients subsequently underwent surgery and reported a pathological CR in the irradiated sites. Grade 3–4 toxicities rate was 30%. With a median follow-up of 29 months (range: 12–49 months), 2/10 progression of disease in irradiated sites and 3/5 in non-irradiated sites were observed. Conclusions: The very high response rate requires urgent verification in a larger patient series.