Gianpiero Catalano

Three-dimensional conformal or stereotactic reirradiation of recurrent, metastatic or new primary tumors. Analysis of 108 patients.

Purpose:To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques.Patients and Methods:108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy.Results:Median follow-up was 7 months (range, 1–50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent.Conclusion:A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.Ziel:Analyse der Therapieergebnisse nach Rebestrahlung von Rezidivtumoren, Metastasen oder Zweittumoren mit dreidimensionaler Konformationsstrahlentherapie (3D-CRT) oder stereotaktischer Radiotherapie (SRT).Patienten und Methodik:108 zwischen 01/2002 und 01/2005 am European Institute of Oncology, Mailand, Italien, rebestrahlte Patienten wurden analysiert. Bei Erstdiagnose lagen Tumoren der Mamma, der Lunge, des HNO-Bereichs sowie urologische und andere Tumoren vor. 27 Patienten (25%) wurden mit kurativer Zielsetzung und 81 (75%) in palliativer Absicht mit einer mittleren Gesamtdosis von 23 Gy bestrahlt.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 7 Monate (1–50 Monate). Ansprechen, Stabilisierung und Progression wurden bei 33%, 36% und 17% der Patienten beobachtet. 15 Patienten konnten nicht ausgewertet werden. Schwerwiegende Toxizität wurde nicht beobachtet. Das mediane Gesamtüberleben lag bei 32,6 Monaten und war bei Patienten, die in kurativer Absicht behandelt wurden, länger.Schlussfolgerung:Ein kleiner Teil der Patienten kann durch eine Rebestrahlung in Remission gebracht werden, in vielen Fällen lässt sich eine Palliation erreichen. Die gute Verträglichkeit der Rebestrahlung bei Verwendung moderner Techniken ermöglicht zukünftig die Applikation einer höheren Dosis und damit evtl. auch eine weitere Verbesserung der Ergebnisse.

Three-Dimensional Conformal or Stereotactic Reirradiation of Recurrent, Metastatic or New Primary Tumors

Purpose:To analyze the outcome of reirradiation of recurrent/metastatic or new primary tumors with three-dimensional conformal (3D-CRT) or stereotactic (SRT) techniques.Patients and Methods:108 patients reirradiated between 01/2002 and 01/2005 at the European Institute of Oncology, Milan, Italy, were analyzed. Primary diagnosis included breast, lung, head/neck, urologic tumors, and other primaries. Curative and palliative intent were applied to 27 (25%) and 81 patients (75%), respectively. 3D-CRT and SRT were employed in 57 (53%) and 48 patients (44%), respectively, up to a mean dose of 23 Gy.Results:Median follow-up was 7 months (range, 1–50 months). Response, stabilization, and progression were observed in 33%, 36%, and 17% of patients, respectively (15 patients were not evaluable). No severe toxicity was reported. Median overall survival amounted to 32.6 months and was longer in patients treated with curative intent.Conclusion:A small portion of patients can be cured with a second course of radiotherapy, and in many cases, palliation can be obtained. Low toxicity of reirradiation with use of modern techniques should allow for the delivery of higher doses and, in consequence, lead to an improvement in reirradiation outcome.Ziel:Analyse der Therapieergebnisse nach Rebestrahlung von Rezidivtumoren, Metastasen oder Zweittumoren mit dreidimensionaler Konformationsstrahlentherapie (3D-CRT) oder stereotaktischer Radiotherapie (SRT).Patienten und Methodik:108 zwischen 01/2002 und 01/2005 am European Institute of Oncology, Mailand, Italien, rebestrahlte Patienten wurden analysiert. Bei Erstdiagnose lagen Tumoren der Mamma, der Lunge, des HNO-Bereichs sowie urologische und andere Tumoren vor. 27 Patienten (25%) wurden mit kurativer Zielsetzung und 81 (75%) in palliativer Absicht mit einer mittleren Gesamtdosis von 23 Gy bestrahlt.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 7 Monate (1–50 Monate). Ansprechen, Stabilisierung und Progression wurden bei 33%, 36% und 17% der Patienten beobachtet. 15 Patienten konnten nicht ausgewertet werden. Schwerwiegende Toxizität wurde nicht beobachtet. Das mediane Gesamtüberleben lag bei 32,6 Monaten und war bei Patienten, die in kurativer Absicht behandelt wurden, länger.Schlussfolgerung:Ein kleiner Teil der Patienten kann durch eine Rebestrahlung in Remission gebracht werden, in vielen Fällen lässt sich eine Palliation erreichen. Die gute Verträglichkeit der Rebestrahlung bei Verwendung moderner Techniken ermöglicht zukünftig die Applikation einer höheren Dosis und damit evtl. auch eine weitere Verbesserung der Ergebnisse.

Modulation of Epidermal Growth Factor Receptor Status by Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer Is Rare

PURPOSE To determine whether epidermal growth factor receptor (EGFR) expression in non-small-cell lung cancer (NSCLC) is modulated by chemotherapy and to assess the agreement of EGFR status between mediastinal nodes and the primary tumor after chemotherapy. PATIENTS AND METHODS Patients with NSCLC stage IIIa/b pN2/3 confirmed by mediastinoscopy or mediastinostomy were treated with at least three cycles of chemotherapy before undergoing surgery. EGFR expression was evaluated on mediastinal nodes at the time of initial diagnosis and on both the primary tumor and residual metastatic nodes after treatment. RESULTS EGFR expression determined on 138 of 164 patients who underwent mediastinoscopy or mediastinostomy was 0 (22 patients), 1+ (27 patients), 2+ (28 patients), and 3+ (61 patients). Fifty-four patients of 164 received chemotherapy followed by surgery. Of the 89 of 138 patients with EGFR score of 2+/3+ at the time of diagnosis, 34 patients underwent surgery after induction chemotherapy. None changed to zero EGFR immunoreactivity, with 29 patients (88%) maintaining a score of 2+/3+. Of the 22 of 138 patients with no EGFR expression at the time of diagnosis, six underwent surgical resection after induction chemotherapy. Of these six patients, four changed their EGFR expression from an EGFR score of 0 to 2+/3+. After treatment, the agreement of EGFR status between tumor and nodes in the subgroup of patients with EGFR score 2+/3+ was 89% to 92%. CONCLUSION Our data suggest a very good agreement of EGFR status before and after chemotherapy in EGFR-positive NSCLC. Induction chemotherapy can induce EGFR expression in occasional EGFR-negative tumors.

Radiotherapy of liver malignancies. From whole liver irradiation to stereotactic hypofractionated radiotherapy

Aims and background Until recently radiotherapy of hepatic malignancies has played a limited role due to the well-known limited radiotolerance of the liver. The aim of this paper is to review the available data on the risk of radiation-induced liver disease (RILD) and to define the modern role of radiotherapy in the management of patients with metastatic or primary liver malignancies. Methods The advent of three-dimensional conformal treatment planning with dose-volume histogram analysis has made the study of partial liver irradiation possible. Limited portions of the liver may withstand high doses of radiation with minimal risk of RILD. Patients with solitary unresectable liver tumors may be treated with high-dose radiotherapy with curative intent. Recently, the feasibility of stereotactically guided treatment techniques with a single fraction or few treatment sessions has been explored in numerous institutions. Results The radiation tolerance of the whole liver found by several investigations is in the order of approximately 30 Gy, which seriously restricts its clinical application. The role of whole liver irradiation therefore appears of limited benefit in the palliation of patients with multiple liver metastases. The use of three-dimensional conformal techniques has made partial liver irradiation possible to doses in the 70–80 Gy range with conventional fractionation. At least two published series have reported improved local control and survival rates with dose escalation with three-dimensional conformal radiotherapy in patients with unresectable liver metastases. Similar outcomes have been recently reported with single dose (or hypofractionated) stereotactic radiotherapy both in metastatic and primary hepatic malignancies with minimal morbidity. Accurate target delineation and treatment reproducibility are the key to the success of this novel treatment approach, and specific treatment planning techniques and patient setup procedures must be developed to implement it. Conclusions Stereotactic high-dose radiotherapy is technically feasible for the treatment of inoperable liver malignancies, with the potential of high local control and low morbidity. Definitive evidence on the clinical advantages of this technique over other more established treatments can only be gathered from well-designed clinical studies.

Linac-based stereotactic body radiotherapy for oligometastatic patients with single abdominal lymph node recurrent cancer

Objectives:To evaluate stereotactic body radiotherapy (SBRT) for single abdominal lymph node cancer recurrence. Methods:Inclusion criteria for this retrospective study were as follows: adult oligometastatic cancer patients with single abdominal lymph node recurrence that underwent SBRT but not other local therapy, written informed consent for treatment. Previous radiotherapy or concomitant systemic therapy were allowed. Toxicity and tumor response were evaluated using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Scale and Response Evaluation Criteria in Solid Tumors. Results:Sixty-nine patients (94 lesions) underwent SBRT (median 24 Gy/3 fractions). Primary diagnosis included urological, gastrointestinal, gynecologic, and other malignancies. Concomitant systemic therapy was performed in 35 cases. Median follow-up was 20 months. Two grade 3 acute and 1 grade 4 late toxicity events were registered. Complete radiologic response, partial response, stabilization, and progressive disease were observed in 36 (44%), 21 (26%), 20 (25%), and 4 (5%) lesions, respectively, out of 81 evaluable lesions. Response rates were similar when analysis was restricted to lesions treated with exclusive SBRT (no concomitant therapy). Actuarial 3-year in-field progression-free interval, progression-free survival and overall-survival rates were 64.3%, 11.7%, and 49.9%, respectively. Overall-survival rates were significantly higher in favorable histology cases (prostate and kidney tumors). Pattern of failure was predominantly out-field. Conclusions:SBRT is a feasible approach for single abdominal lymph node recurrence, offering excellent in-field tumor control with low-toxicity profile. Future studies are warranted to identify the patients that benefit most from this treatment. The optimal combination with systemic treatment should also be defined.

Analysis of mandibular dose distribution in radiotherapy for oropharyngeal cancer: dosimetric and clinical results in 18 patients

BACKGROUND AND PURPOSE The relationship between the radiation dose and the risk of the osteoradionecrosis is well known. However, the dose to the mandible is not routinely assessed in the radiotherapy for head and neck cancer. The aim of our study was to analyze the mandibular dose distribution in the patients administered curative radiotherapy for squamous cell carcinoma of the oropharynx. Moreover, the clinical results have been analyzed. MATERIAL AND METHODS We examined the clinical records and treatment plans in 18 patients treated with bifractionated radiotherapy for stage II-IV oropharyngeal cancer. In 17 patients, the total radiotherapy dose prescribed in the International Committee of Radiation Units and Measurements (ICRU) reference point was 74.4 Gy administered in 62 fractions (1.2 Gy twice daily with 6h interfraction interval) and one patient received a dose of 75.6 Gy. The whole dose to the mandibular-orophryngeal region was delivered with 6 MV photons. The mandible was contoured manually on computed tomographic scans and the point doses at the both mandibular condyles, ascending ramus, mental symphysis, molar and retromolar regions were assessed. Moreover, the cumulative dose-volume histograms (DHVs) were evaluated. The median follow-up period for alive patients is 30 months (range, 21-44+ months). RESULTS Tumor remission was observed in 17 patients: in 11 cases, complete remission was achieved and in six cases, only partial remission was possible. One patient was lost to follow-up before the first response evaluation. The median survival for all patients is 22 months (range, 3-44+ months). Ten patients are alive and seven died. In six cases, the cause of death was head and neck tumor and in one died due to pancreatic cancer (second primary). No late bone post-radiation complication was seen. The highest radiotherapy doses were observed in the retromolar regions. The mean percentage doses at the right and left retromolar regions were 101.3+/-3.8% (range, 90.2-109.1%) and 101.7+/-2.5% (range, 95.2-105.8%), respectively. Lower doses were seen in ascending ramus (the mean percentage doses at right and left ascending ramus were 97.3+/-8.5% and 97.8+/-7.6%, respectively), the molar regions (the mean percentage doses at right and left molar regions were 86.0+/-13.5% and 88.1+/-12.9%, respectively), and at the mandibular condyles (the mean percentage doses at the right and left mandibular condyles were 72.6+/-18% and 77.0+/-16.5%, respectively). The volume of the mandible ranged from 60.1 to 110.1cm(3) (a mean of of 82.3 cm(3)). In all patients, the maximum dose absorbed in the mandible was higher than the dose prescribed in the ICRU point and the mean maximum dose absorbed in the mandible was 105.7+/-2.1% (range, 102.4-110.6%). The percentage of mandibular volume receiving a dose higher than prescribed was 28.6+/-14.9% (range 10.2-58.1%). The area underlying the DVH curve, the maximum mandibular doses and the retromolar doses did not appear to statistically depend on use of wedge or mandibular volume. CONCLUSIONS Radiotherapy for oropharyngeal cancer is associated with high doses to the retromolar mandibular regions (the dose can be higher than prescribed in the ICRU reference point), ascending ramus and molar regions. Lower doses are absorbed at the condyles and mental symphysis. The single dose point (for example, the ICRU reference point) could be not used as a representative for the mandibular dose. In our small series of patients treated with hyperfractionated irradiation, these dose heterogeneities were not correlated to the patient- and treatment-related factors and are not related to the increased risk of late bone complications. The clinical relevance of mandibular dose distribution remains to be established in larger series of patients treated with conventionally and unconventionally fractionated irradiation.

Adjuvant Surgery after Carboplatin and VP16 in Resectable Small Cell Lung Cancer

Introduction: The real benefit of surgical treatment of small cell lung cancer (SCLC) has never been demonstrated, mainly because of the rarity of surgical cases and the difficulty in comparing surgical and medical series for the different classifications systems used by surgeons (tumor, node, metastasis) and medical oncologists and radiotherapists (Veterans Administrations Lung Cancer Study Group). Materials and Methods: We prospectively assessed the utility of surgery after chemotherapy (carboplatin plus VP16 with or without ifosfamide) with or without radiotherapy in 23 patients with preoperative diagnosis of resectable stage I to IIIA SCLC. A median of three (range: three to six) courses of chemotherapy were administered. Five pneumonectomies, 12 lobectomies (seven sleeve resections), and two segmentectomies were performed, and all except one received radical lymph node dissection. Four (17%) patients received exploratory thoracotomy. Nine (39%) patients received postoperative thoracic radiotherapy. Results: Pathological stages were complete response in four patients, stage I in seven patients, stage II in seven patients, and stage III in five patients. Thirty-day morbidity and mortality were 9% and 0%, respectively. Surgery-related mortality at 90 days was 9%. Median follow-up was 19 months. Overall and local relapse rates were 52% and 17%, respectively. Median overall and disease-free survival were 24 and 12 months. Patients with complete response or pathological stage I had a significantly better Kaplan–Meier survival and lower incidence of relapse than those with more advanced pathological stage (p = 0.025 and 0.027, respectively, log rank). Conclusions: Survival after chemotherapy and surgery in the series correlated with pathological but not pretreatment stage. Only patients with pathological stage 0 or I disease seem to benefit from surgical resection.

Lymph node metastases of Merkel cell carcinoma from unknown primary site: report of three cases

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine skin carcinoma. It usually affects sun-exposed skin of white elderly people. MCC is characterized by a high incidence of early locoregional relapse and distant metastases. Because of its rarity and the resulting lack of prospective randomized trials, data regarding the optimal treatment of MCC are limited. Despite aggressive multimodality treatment, the prognosis of patients bearing MCC is often poor. We report three cases of lymph node metastases of MCC with unknown primary sites. Two patients died 17 and 28 months after diagnosis due to brain and pancreatic metastases, respectively, without evidence of cutaneous disease. The third patient is alive and free of tumor at 16 months from the diagnosis. After an accurate diagnosis of lymph node metastases from MCC, the absence of a primary tumor at complete initial evaluation and during adequate follow-up can confirm this particular clinical scenario. The prognosis seems to be analogous to that of cases with similar disease stage (lymph node involvement) but a known primary site.

Deep inspiration breath‐hold technique guided by an opto‐electronic system for extracranial stereotactic treatments

The purpose of this work was to evaluate the intrapatient tumor position reproducibility in a deep inspiration breath‐hold (DIBH) technique based on two infrared optical tracking systems, ExacTrac and ELITETM, in stereotactic treatment of lung and liver lesions. After a feasibility study, the technique was applied to 15 patients. Each patient, provided with a real‐time visual feedback of external optical marker displacements, underwent a full DIBH, a free‐breathing (FB), and three consecutive DIBH CT‐scans centered on the lesion to evaluate the tumor position reproducibility. The mean reproducibility of tumor position during repeated DIBH was 0.5±0.3mm in laterolateral (LL), 1.0±0.9mm in anteroposterior (AP), and 1.4±0.9mm in craniocaudal (CC) direction for lung lesions, and 1.0±0.6mm in LL, 1.1±0.5mm in AP, and 1.2±0.4mm in CC direction for liver lesions. Intra‐and interbreath‐hold reproducibility during treatment, as determined by optical markers displacements, was below 1 mm and 3 mm, respectively, in all directions for all patients. Optically‐guided DIBH technique provides a simple noninvasive method to minimize breathing motion for collaborative patients. For each patient, it is important to ensure that the tumor position is reproducible with respect to the external markers configuration. PACS numbers: 87.53.Ly, 87.55.km

Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study.

Purpose:To evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA–IIIB non-small cell lung cancer (NSCLC).Patients and Methods:iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions.Results:From February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08).Conclusion:In this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC.Ziel:Untersuchung der Durchführbarkeit und Toxizität einer dreimal täglichen Strahlentherapie (3tdRT) nach Induktionschemotherapie (iCT) bei nichtkleinzelligem Bronchialkarzinom (NSCLC) im Stadium IIIA–IIIB.Patienten und Methodik:Die iCT umfasste drei Zyklen Cisplatin und Gemcitabin. Bei Patienten, die auf die iCT ansprachen, wurde eine operative Therapie erwogen. Nach Planung der definitiven bzw. postoperativen 3tdRT wurden Gesamtdosen von 54,4 bzw. 64,6 Gy in drei Fraktionen pro Tag verabreicht.Ergebnisse:Zwischen Februar 1998 und Oktober 2000 erhielten 37 Patienten eine radikale (n = 18) oder postoperative 3tdRT (n = 19). Die Toxizität beschränkte sich auf eine akute Ösophagitis RTOG-Grad 2 (25 Patienten, 67,6%) und 3 (vier Patienten, 10,8%); eine späte Ösophagitis Grad 3 wurde nicht beobachtet. Bei einem Patienten zeigte sich eine späte Lungentoxizität in Form einer Grad-3-Pneumonie. Zwischen akuter Ösophagustoxizität und bestrahltem Ösophagusvolumen oder krankheits- und therapiebezogenen Faktoren ergab sich keine Korrelation. Dagegen fanden sich eine signifikante Korrelation für das Tumorstadium (IIIA vs. IIIB; p = 0,03) und eine Tendenz für den Lymphknotenbefall (N2 vs. N3; p = 0,08).Schlussfolgerung:In dieser Studie zur 3tdRT nach iCT erwies sich die Kombinationstherapie aufgrund ihrer geringen Toxizität als geeignet. Die eingeschränkte statistische Aussagekraft lässt keine Bestimmung prädiktiver Faktoren für Häufigkeit und Schwere einer strahlenbedingten Ösophagitis zu; weitere Studien sind erforderlich, um den Einfluss von Volumen- und Dosisparametern zu klären. Analysen von Rezidivierungsverhalten und Überleben könnten die Wirksamkeit dieses Verfahrens bei lokal fortgeschrittenem NSCLC bestätigen.