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The recurrence of cancer sometimes poses a difficult problem for the clinician. The conventional treatment has already failed, and further treatment with radiation is often not advisable. In some cases, if the tumor is not operable and alternative chemical or hormonal therapies have failed, it may be possible to use hyperthermia alleviate the symptoms of cancer. The authors report their experience with 60 cancerous lesions for which conventional therapy had failed. Each lesion was then treated using a microwave or radiofrequency device to raise the temperature within the cancer to 42 degrees centigrade twice a week. A total of 6, 8, or 10 heating sessions were administered; 10 complete responses were observed. Although only 15 of the 60 lesions were adenocarcinomas, these cancers accounted for 6 of the 10 complete responses. In contrast, while 39 of the 60 cancers were squamous cell carcinomas, they accounted for only 3 of the 10 complete responses. Furthermore, long term local control, lasting over 54 months, was achieved for four patients with adenocarcinoma. The patients with other cancer types died within two years. These results indicate that hyperthermia may be a useful treatment for appropriately selected patients with adenocarcinoma. For other patients, hyperthermia may be useful for the alleviation of pain. (Consumer Summary produced by Reliance Medical Information, Inc.)

Introduction: Stereotactic body radiation therapy is increasingly used in the treatment of early-stage lung cancers. Guidelines provide indications regarding the constraints to the organs at risk (OARs) and the minimum coverage of the planning target volume but do not suggest optimal dose distribution. Data on dose distribution from the different published series are not comparable due to different prescription modalities and reported dose parameters.Methods: We conducted a review of the published data on dose prescription, focusing on the role of homogeneity on local tumor control, and present suggestions on how to specify and report the prescriptions to permit comparisons between studies or between cases from different centers.Conclusions: To identify the dose-prescription modality that better correlates with oncologic outcomes, future studies should guarantee a close uniformity of dose distribution between cases and complete dose parameters reporting for treatment volumes and OARs.

Stereotactic Ablative Radiotherapy (SABR) has been previously investigated as an alternative to thoracic surgery in patients with a limited number of pulmonary nodules from different primary tumors. We here report the clinical outcomes of a series of consecutive patients homogenously selected and treated with single dose SABR in our Institution. Eligibility criteria were: 1–5 lung metastases, maximum tumor diameter <50 mm, absent or controlled extra-thoracic disease, adequate pulmonary function, no prior radiotherapy, performance status ECOG 0–1. All patients were treated with a single dose of 26 Gy prescribed to the 80% isodose, by 3D-CRT or by IGRT-VMAT. Follow-up consisted of clinical evaluation and periodic CT scans. Primary endpoints were Local Control (LC), toxicity and Progression-Free Survival (PFS). Secondary endpoints were Cancer-Specific Survival (CSS) and Overall Survival (OS). Out of 102 patients treated with SABR between october 2003 and october 2011, we selected 67 patients for a total of 90 lesions. Main primary tumor sites were lung and colon-rectum (37.3% and 43.3% of lesions, respectively). Median follow up time was 24 months. Treated metastasis progression at SABR site was observed in 10 lesions (11.1%), and actuarial LC rates at 1 and 2 years were respectively 93.4% and 88.1%. Systemic failure occurred in 37 patients (55.2%) at a median interval of 8 months after SABR. PFS rates were 72% and 55.4% at 1 and 2 year. Seven patients had grade 1 (10.4%) and 8 grade 2–3 late radiological toxicity (11.9%), while 6 experienced late chest wall toxicity (2 rib fractures, 4 chronic chest pain, 8.9%). CSS rates at 1 and 2 years were 90% and 76%, while OS rates were 85.1% and 70.5%, respectively. Median survival time was 40 months. On multivariate analysis, a disease-free interval longer than 24 months was close to significance for a benefit in CSS (p= 0.07; HR 0.34 [95% CI 0.1–1.12]). The study includes a cohort of patients treated with single fraction 26 Gy SABR followed for a prolonged time interval. Single fraction SABR appears to be an effective treatment option, with little observed acute toxicity and limited late toxicity (<15%); its advantages also include a high patients' compliance, a short overall treatment time and an easy combination with systemic therapies. These results might provide supportive evidence to the use of single fraction SABR as a valid and acceptable alternative to surgery for pulmonary metastases from different primary tumors.

Aims and background To evaluate the clinical outcome of a cohort of localized prostate cancer patients treated with 125I permanent brachytherapy at the University of Turin.Methods and study design A retrospective analysis was carried out on 167 consecutive patients with early stage prostate adenocarcinoma who underwent 125I brachytherapy between January 2003 and December 2010. A minimum follow-up of ≥12 months was mandatory for inclusion. Biochemical disease-free survival (defined on the basis of the ASTRO definition and the ASTRO-Phoenix definition) was chosen as the primary end point. Secondary end points were gastrointestinal and genitourinary toxicity (acute and late, defined according to the RTOG scale).Results With a median follow-up of 42 months (range, 13.5–90.7), biochemical disease-free survival at 3 and 5 years was respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and 85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35 ng/ml) were the only factors affecting biochemical disease-free survival both on univariate (P= 0.02 and P= 0.001, respectively) and multivariate analysis (HR 0.024; P= 0.021 and HR 21.6; P= 0.006, respectively). Only 3.6% of patients experienced ≥grade 3 acute urinary toxicity and 5% ≥grade 3 late urinary toxicity. Prior transurethral prostate resection was the only independent predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P= 0.009).Conclusions This mono-institutional series confirmed that brachytherapy is an effective and safe treatment modality for localized prostate cancer, with acceptable short- and long-term morbidity rates.

Aim and background Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial.Materials and methods From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin.Results The 3, 5 and 10-year local-regional recurrence-free survival rates were better in arm II(21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04).Conclusions Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial.

Aims and Background In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable.Methods and Study Design Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients.Results At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pTO) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy.Conclusions For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.

Aims and background Brachytherapy for prostate cancer by means of permanently implanted 125I sources is a well established procedure. An increasing number of patients all over the world are treated with this modality. When the technique was introduced at our institution, radiation protection issues relative to this technique were investigated in order to comply with international recommendations and national regulations. Particular attention was paid to the need for patient shielding after discharge from hospital.Methods The effective and equivalent doses to personnel related to implantation, the effective dose to patient relatives as computed by a developed algorithm, the air kerma strength values for the radioactive sources certified by the manufacturer compared with those measured by a well chamber, and the effectiveness of lead gloves in shielding the hands were evaluated.Results The effective dose to the bodies of personnel protected by a lead apron proved to be negligible. The mean equivalent doses to the physician's hands was 420 μSv for one implant; the technician's hands received 65 μSv. The mean air kerma rate measured at the anterior skin surface of the patient who had received an implant was 55 μGy/h (range, 10–115) and was negligible with lead protection. The measured and certified air kerma strength for 125I seeds in RAPID Strand corresponded within a margin of ± 5%. The measured attenuation by lead gloves in operative conditions was about 80%. We also defined the recommendations to be given to the patient at discharge.Conclusions The exposure risks related to brachytherapy with 125I to operators and public are limited. However, alternation of operators should be considered to minimize exposure. Patient-related measurements should verify the dose rate around the patient to evaluate the need for shielding and to define appropriate radiation protection recommendations.

The current randomized, multicenter, Phase III trial was conducted to determine whether the disease free interval and overall survival of patients with T2–T4,N0–N3,M0 squamous cell carcinoma (SCC) of the oral cavity or oropharynx could be extended through the combination of surgery (and radiotherapy, if required) with perilymphatic recombinant IL-2 (rIL-2). Patients with a resectable T2–T4,N0–N3,M0 SCC of the oral cavity and oropharynx were assigned randomly to receive surgery and radiotherapy or to receive IL-2, surgery, and radiotherapy. Five thousand units of rIL-2 were injected around the ipsilateral cervical lymph node chain daily for 10 days before surgery. After surgery, contralateral 5-day rIL-2 courses were administered monthly for 1 year. The differences in disease free and overall survival between the two groups of patients were evaluated statistically. Two hundred two patients finished the study. No significant complications related to rIL-2 were encountered, and surgery and radiotherapy were not hampered by its prior administration. Multivariate analysis conducted to determine the extent to which survival was influenced by rIL-2 and the other variables showed that rIL-2 significantly lengthened disease free survival (P &lt; 0.01) and that this resulted in longer overall survival (P &lt; 0.03). The data emerging from this trial indicate that perilymphatic administration of low, nontoxic doses of rIL-2 is a simple and manageable way to delay recurrences of SCC. Cancer 2002;95:90–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10654

The treatment of carcinoma of the head and neck in recent years has improved significantly, chiefly thanks to progress in surgery and radiotherapy. Despite these advances, the survival statistics reported in the literature show no appreciable evidence of radical improvement. The aims of this study were to evaluate the impact on survival achieved with the combination of surgical and postoperative radiotherapy in patients with advanced head and neck carcinomas and to identify the prognostic value of several host- and tumor-related factors that can influence the results of combined treatment. We retrospectively reviewed the medical records of 394 patients with stage III and IV carcinoma of the head and neck, of whom 170 (43%) underwent surgery alone and 224 (57%) received combined surgery and postoperative radiotherapy. The 394 patients were stratified for a set of variables including the patient's condition, the characteristics of the tumor, and the modality of treatment. Univariate analysis revealed that coexistent medical diseases, the size and site of the primary lesion, the stage of the tumor, and certain pathologic features had a negative impact on survival. Multivariate analysis showed that the removal of lymph nodes and postoperative radiotherapy can have a positive influence and can improve the prognosis. We compared the survival rates of the patients treated with surgery alone with those of the patients who underwent combined treatment, and we observed that the two survival curves were comparable, even if there was a bias because the combined treatment group consisted of patients with negative prognostic factors. The meaning of these results, compared with data from the literature, has been discussed.

In this study we evaluated the effects of surgical and radiotherapy treatment on local control in 126 patients with malignant tumors of the parotid gland. The most frequently observed malignant tumors were high-grade tumors (68%). Surgical treatment was performed in 81 patients (83.5%). Total conservative parotidectomy was the most frequent procedure (74%), and radiotherapy was performed in 81 patients (83.5%). The global survival rate was approximately 54% at 5 years, whereas disease-free survival was 47% at 5 years. No statistically significant difference in survival rate was found between conservative (52% at 5 years) and radical treatment of the seventh cranial nerve (43% at 5 years). The incidence of recurrent cancer was 25.7% (25 of 97), of which 88% developed during the first 2 years. We report some of the clinical and histologic factors that can influence the prognosis of the disease. (Otolaryngol Head Neck Surg 1999;121:627-32.)

Aims and Background The choice of treatment in limited squamous cell carcinoma of the glottic larynx often depends on individual and tumor factors. Data of the literature clearly show that surgery and radiotherapy tend to give identical results in terms of survival. We examined 196 cases of T1-T2/N0 cancers of the glottic larynx. We review the literature and discuss the indications and the efficacy of the various available treatments.Methods and Study Design 196 consecutive cases of T1-T2/N0 cancers of the glottic larynx were examined. In 54.5% the tumor was confined to the vocal cord; in 38.2% it extended to the anterior commissure, in 4.6% to the arytenoid cartilage and in 2.5% to the floor of the ventricle. We performed partial laryngeal surgery in 41.3% (81 cases). Radiotherapy alone was employed in 58.6% (115 cases).Results In T1a and T1b cases there was no statistically significant difference in 5-year disease-free survival. In T2 cases the NED survival of patients who underwent partial laryngectomies (90% of cases) was significantly better (P <0.05) than among patients given radiotherapy (73%). NED survival at 5 years in patients with the primary tumor on a vocal cord, ventricle or anterior commissure was 78%, 80% and 81%, respectively, with no statistically significant difference among the various sites. It is possible that involvement of the anterior commissure exposes patients to greater risk of recurrence when radiotherapy alone is used (5 out of 23 cases, 21.7%, compared to 3 out of 52 cases, 5.7%, among our surgically treated patients).Conclusions When the tumor is confined to the vocal cord and mobility is not impaired (T1a), surgery and radiotherapy give comparable results, and the latter yields a better functional outcome. When the anterior commissure is involved, recurrences appear to be less likely after surgery. In T2 glottic carcinoma, surgery gives better results than radiotherapy alone. In any event, the choice of treatment should be patient-specific and based on a careful analysis of the factors involved in each case.

The combination of daily low-dose carboplatin and radiotherapy was studied in 55 patients with inoperable head and neck cancer. All patients were planned to receive 70 Gy plus carboplatin i.v. daily, 45-60 min before radiotherapy. A starting schedule of 30 mg/m2 on days 1 through 5, weeks 1, 3, 5 and 7 was administered to 17 patients; an escalating daily dose, up to 55 mg/m2 was given to 38 additional patients. Up to a daily dose of 45 mg/m2 only 4.4% of the patients developed grade 3 leukopenia; on the contrary, grade 3 and 4 leukopenia was seen in 62.5% of patients receiving 50 mg/m2 or more. Mucositis was the major nonhaematologic toxicity and seemed to be dose-dependent. At the end of the loco-regional treatment there were 33 (61.1%) CR and 17 PR; the most effective total carboplatin dose seemed to be 40-45 mg/m2. After surgical salvage the number of CRs increased to 37 (68.5%). One-and 2-year loco-regional control rates were 64% and 53% respectively. One- and 2-year actuarial survival rates were 71% and 53% respectively; the corresponding rates of disease-free survival were 60% and 43%. There was a strong correlation nodal status and both survival and disease-free survival.

Aims and background The metastatic spread of squamous cell carcinoma of the head and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in terms of survival. We have used multivariate analysis to identify the possible prognostic significance of a number of clinical and pathological characteristics in relation to possible involvement of the cervical lymph nodes in a series of 396 patients.Method 396 patients with SCCHN were studied. Variables regarding the patient, the carcinoma and histology were analysed by multivariate analysis using BMDP's PLR programme.Results Some variables appear to represent predisposing factors for tumor spread to the lymph nodes: tumor site (supraglottic larynx: P=0.005; base of the tongue: P=0.02; hypopharynx: P=0.02), grading (P=0.001), and a number of histological parameters (lower degree of histological differentiation: P=0.001; vascular permeation: P=0.04; perineural invasion: P<0.05; prevalently plasmocytic infiltrate: P<0.05).Conclusion The identification of cases at risk for metastasis can be improved by the assessment of prognostic factors, with a consequent improvement in treatment strategies.

The introduction of new treatment methods has stimulated the identification of further prognostic factors capable of defining the clinical and biological characteristics of the tumor type in question and improving treatment programming. The aim of this study was to identify which characteristics of the host and tumor are of prognostic value in relation to the onset of locoregional tumor recurrence. A total of 396 patients were studied. The tumor site distribuition can be summarized as follows: 267 laryngohypopharyngeal, 74 oropharyngeal, 55 oral cavity. Variables regarding patient, tumor and histology were evaluated for the purpose of analysis. Multivariate analysis of these prognostic factors was performed using PLR software by BMDP. Mean tumor recurrence time was 19 months. Seventeen of the 29 variables anlysed did not influence the probability of tumor recurrence. Two variables reduced the risk of tumor recurrence: age >61 years and abundant and prevalently lymphocytic intra- and peritumoral infiltrate. The study of tumor recurrence onset mechanisms is justified by its impact on the evolution of disease. The use of multivariate analysis in this study showed that some clinical and pathological characteristics of squamous cell carcinoma of the head and neck have a statistically significant impact on tumor recurrence.