Non-surgical organ preservation strategies for locally advanced laryngeal tumors: what is the Italian attitude? Results of a national survey on behalf of AIRO and AIOM.

Chemoradiotherapy is the treatment mostly used as organ preservation (OP) strategy worldwide in advanced laryngo-hypopharyngeal cancer. Due to the not homogeneous results of the literature data regarding the pre-treatment assessment and treatment schedule in this setting of patients, the Italian societies of radiation oncology and medical oncology surveyed (by an online survey) their memberships regarding the Italian attitude on larynx preservation in clinical practice. The survey outline addressed different items such as: demographics (11 items), pre-treatment evaluation (12 items), treatment schedules (10 items) and outcomes (3 items). The survey was filled in by 116 clinical oncologists (64 % radiation and 36 % medical oncologists). Results highlighted that pretreatment evaluation was not homogeneous among the respondents. The treatment of choice for the OP program resulted the concurrent chemoradiotherapy (66 %). Induction chemotherapy was proposed mostly in case of aggressive tumors such as advanced stage (T4 or N3) and/or unfavorable primary sites (hypopharynx). Moreover, after induction chemotherapy, for responders patients most participants (46 %) proposed concurrent chemoradiotherapy, while 18 and 19 % proposed radiotherapy alone or radiotherapy and cetuximab, respectively. For patients with stable disease after induction chemotherapy, the respondents declared to suggest surgery, radiotherapy and cetuximab or radiotherapy alone in 38, 32 and 15 % of cases, respectively. Results of the present survey highlighted the variability of therapeutic approaches offered in clinical practice for patients candidate to a larynx OP program. Analysis of abovementioned results may give the chance to modify some clinical attitudes and create the background for future clinical investigation in this field.

Is there a role for postoperative radiotherapy following open partial laryngectomy when prognostic factors on the pathological specimen are unfavourable? A survey of head and neck surgical/radiation oncologists.

Our aim was to survey the opinions of Italian radiation and ENT oncologists regarding the role of postoperative radiotherapy (PRT) and the appropriate dose to be given to patients with remnant larynx (RL) after open partial laryngectomy (OPL). The radio-oncologists (ROs) of the Italian Radiation-Oncologist Association (AIRO) and the ENTs of the Head-Neck Oncology Society (AIOCC-IHNS) were contacted through a SurveyMonkey online interface questionnaire. There were 148 usable responses. The majority of ROs recommended PRT in the case of positive/close margins (R(+)/R(close)) or in the case of initial involvement of thyroid cartilage (pT3(tci)). In the same cases, ENTs prefer a "watch and wait" policy (w&w). Both disciplines recommended w&w in the case of negative margins (R(-)). Finally, the majority of RO s recommended irradiating RL with 62-66 Gy in R(+), with 56-66 Gy (61.4%) in R(close) and with 56-60 Gy (34%) in pT3(tci). In Conclusion, OPL raises new considerations about PRT.

The role of neck dissection after radical chemoradiation for locally advanced head and neck cancer: should we move back?.

Until a few decades ago neck dissection (ND) was the standard surgical approach for node-positive tumours. Nowadays patients with locally advanced head and neck cancer can be treated with definitive chemoradiation (CRT), which includes the treatment of the neck; however, results on residual viable tumour after conservative treatment are heterogeneous and depend on initial node stage and primary treatment. Many authors accept adjuvant surgery in patients with N2-3 disease. Regardless of the results of upfront CRT, even if there is no evidence of lymph node metastases, when the risk for persistent positive neck nodes exceeds 15-20%, elective ND might be indicated. However, despite the diffusion of innovative technologies and therapies, there are controversies about both response evaluation and surgical management of initially involved neck nodes after definitive CRT and organ preservation treatment. In this paper we will analyse state of art of neck evaluation after CRT and discuss the role of ND.

The role of antiangiogenic agents in the treatment of head and neck cancer.

Despite progress in the treatment of locally advanced head and neck squamous cell cancer (HNSCC), the prognosis remains dismal and 5-year survival does not exceed 40%. In metastatic and recurrent disease, in spite of the introduction of cetuximab in combination with platinum and fluorouracil, the median overall survival rate remains lower than 11 months. There are many possible reasons for these disappointing results including acquired drug resistance and tumor hypoxia. Angiogenesis plays an important role in HNSCC development and proliferation. Promising preclinical results with antiangiogenic therapies have engendered a number of clinical trials, but so far there have not been any conclusive results on the value of such treatments. This paper aims to review the role of angiogenesis in head and neck cancer and to suggest future perspectives.

Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposals for a revised grading system and consensus management guidelines.

BACKGROUND: Radiation dermatitis developing in patients receiving cetuximab concomitantly with radiotherapy for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is now recognized to have different pathophysiological and clinical characteristics to the radiation dermatitis associated with radiotherapy or concomitant chemotherapy and radiotherapy. Current grading tools were not designed to grade this type of radiation dermatitis; their use may lead to misclassification of reactions and inappropriate management strategies, potentially compromising cancer treatment. PATIENTS AND METHODS: An advisory board of seven leading European specialists (three medical oncologists, three radiation oncologists and a dermatologist) with extensive experience of the use of cetuximab plus radiotherapy produced consensus guidelines for the grading and management of radiation dermatitis in patients receiving cetuximab plus radiotherapy. RESULTS: Modifications to the current, commonly used National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.3 for grading radiation dermatitis were proposed. Updated management guidelines, building on previously published guidelines from 2008, were also proposed. CONCLUSIONS: The proposed revisions to the grading system and updated management guidelines described here represent important developments toward the more appropriate grading and effective management of radiation dermatitis in patients receiving cetuximab plus radiotherapy for LA SCCHN.

Radiation-induced pemphigus vulgaris of the breast.

Pemphigus vulgaris is a rare autoimmune mucocutaneous bullous disease. Patients with a history of pemphigus vulgaris - who need radiotherapy - may show a long lasting bullous cutaneous manifestation, typical of pemphigus, within radiation fields. The literature describes fewer than 20 radio-induced cases. While systematic corticosteroid therapy has proven to be useful, topical treatment used in association with corticosteroid therapy is rarely described. To our knowledge the use of modern dressing products has never been described. We report our experience in a case in which modern dressing products were usefully associated to systemic therapy.

The Role of p53 and MDM2 in Head and Neck Cancer.

Head and neck cancer is a complex disorder that includes mostly squamous cell carcinomas that can develop in the throat, larynx, nose, sinuses, and mouth. Etiopathogenesis is due to tobacco and alcohol consumption and to infection by human papillomavirus (HPV) type 16/18. Tumors often develop within preneoplastic fields of genetically altered cells. Most head and neck cancers result from multistep accumulation of genetic alterationsm resulting in clonal outgrowth of transformed cells. These DNA changes are caused by a variety of mechanisms like endogenous mutations and exogenous mutations. Dysregulated molecular pathway includes alterations of critical inhibitor of cyclin CDK complexes, inactivating mutations of p53 gene, and activation of oncogenes and growth factors. This paper attempts to review the role of p53 and MDM2 genetic aberrations and pathways in head and neck cancer.

External radiation therapy boost to the vaginal vault: feasibility of intracavitary dosimetry using a commercial diode system.

PURPOSE: An overall check of the whole dosimetry procedure by intracavitary in vivo dosimetry, using n-type silicon diode dosimeter, was performed during 6-MV x-ray irradiation of the vaginal vault. The dose delivered to the isocenter by all treatment fields was evaluated. METHODS AND MATERIALS: The diode dosimeter was calibrated against an ion chamber and tissue maximum ratio, field size factor, SSD factor, and temperature dependence studies were performed. Diode system accuracy, linearity, and reproducibility were also tested. Patients' dose data were collected and comparision was made with respect to treatment-planning dose calculations. Ten patients with cervical cancer and endometrial cancer were treated with surgery and irradiation. During the boost to the vaginal vault, a diode was inserted by an intravaginal device and the vaginal vault was the isocenter of the four fields. The field size generally was not larger than 10 x 10 cm2. RESULTS: Diode-measured "tissue maximum ratio" agreed to within 1% with those measured with an ion chamber in field from 7 x 7 to 10 x 10 cm2. The diode also exhibited a temperature dependence of 0.1% degrees C(-1). For 10 patients treated with a 6-MV beam, the agreement with treatment-planning dose calculations was shown to be better than +/-4%. CONCLUSION: The good accuracy and reproducibility of the diode system shows that determination of the dose at isocenter, for patients treated in the pelvic region, can be performed with n-type diodes accurately. On the other hand, in the vaginal vault boost, external-beam radiotherapy is delivered accurately and in vivo dosimetry is really not indicated.

Supraclavicular lymph node metastases (SLM) from breast cancer as only site of distant disease: has radiotherapy any role?

BACKGROUND: Supraclavicular lymph node metastases (SLM) as the only site of metastatic disease from breast cancer is a rare and a poor prognostic event. In order to evaluate the role of Radiotherapy (RT) with "radical dose" to the supraclavicular fossa, we carried out a non randomized clinical trial comparing systemic therapy alone to integrated and aggressive treatment (systemic therapy plus radiotherapy). The primary end-point was time to progression (TTP). The second end-point was the overall survival (OS). METHODS: From 1/1/1989 to 31/12/1994 37 patients (with or without the presence of locoregional disease) were enrolled into two arms, of the study, but were allowed, when giving their consent, to change the arm of the study which they had been originally allotted to. Arm A, 18 patients, 15 evaluable: chemo +/- hormonotherapy for 6 courses; after the second course, if local progression disease was present, the pts. were submitted to RT and removed from the study (3 patients). Arm B, 19 patients all evaluable: chemo +/- hormonotherapy for 3 courses followed by RT with "radical" dose. Results were analyzed on 30/11/1995 and no interim analysis was performed. The potential median follow up for all patients was 56.5 months (range 11-83 months): for Arm A 61 months (range: 12-82); for Arm B 53 months (range: 11-83). The two groups were homogeneous and balanced, without statistical differences. RESULTS: Median TTP was 12.5 months in Arm A and 19.5 months in Arm B (p = 0.064). Median overall survival (OS) was 27.5 months in Arm A and 48 months in Arm B. T-status to the time of the diagnosis was found to be independent prognostic factor for TTP (p = 0.0029). Disease-free interval from diagnosis to recurrence was found to be a significant prognostic factor for OS (p = 0.009). CONCLUSION: The results in Arm B demonstrated the opportunity of a long term control in this subset of patients. Therefore we suggest the start of a wider multicenter study in order to define the biological significance of SLM, its importance in staging breast cancer and to consider the optimum treatment.

[Antalgic radiotherapy in lumbosacral carcinomatous neuropathies]. / La radioterapia antalgica nelle neuropatie carcinomatose lombosacrali.

Lumbosacral carcinomatous neuropathy (LCN) may be caused by infiltration or compression of the lumbosacral plexi and nerves from intrapelvic or paraaortic neoplasms. The authors submitted 23 patients complaining of LCN with CT documented intrapelvic or paraaortic tumors to palliative radiotherapy. Megavoltage external beam irradiation was administered using a 6-MV linear accelerator. Treatment field sizes ranged from 56 cm2 to 235 cm2 (mean: 150.54 cm2) and encompassed only the site where the disease involved the lumbosacral plexus or its branches. > or = 3 Gy/day fractions were used. Twenty-one of 22 assessable patients (95.4%) obtained LCN pain relief; 19 (86.3%) obtained complete LCN pain relief. The median time to pain progression (TPP) was 150 days (range: 39-510 days). The median survival was 165 days. Seven patients were LCN pain-free at death. Two patients are alive and LCN pain-free. The remaining 12 patients had recurrent LCN pain: four of them were reirradiated at the site of previous neuropathy and only two had partial relief again. The authors conclude that it is advisable to submit to palliative radiotherapy the inoperable disseminated and/or recurrent cancer patients complaining of LCN, to use large fractions not to occupy the extant time of their already short life-expectancy, and to design small fields to avoid acute side-effects.

Carcinomatous solitary pulmonary nodules: evaluation of the tumor-bronchi relationship with thin-section CT.

To investigate the value of computed tomography (CT) for depicting the relationship between carcinomatous solitary pulmonary nodules and the bronchial tree and predicting the results of various bronchoscopic biopsy techniques, the authors retrospectively reviewed CT scans from 27 consecutive patients with solitary pulmonary nodules associated with a positive bronchus sign. All patients underwent bronchoscopy and transbronchial biopsy. Macroscopic demonstration of the tumor-bronchi relationship was obtained in 18 patients. Five basic types of tumor-bronchus relationships were identified with CT: (a) bronchus cut off by the tumor, (b) bronchus contained within the tumor, (c) bronchus compressed by the tumor, (d) thickening and smooth narrowing of the bronchus leading to the tumor, and (e) thickening and irregular narrowing of the bronchus leading to the tumor. The diagnostic yield of transbronchial forceps biopsy and bronchial brushing was significantly higher in nodules characterized by a cut-off or contained bronchus. Transbronchial needle aspiration was performed in six patients, and results were positive in five, all of whom had a compressed or thickened bronchus. These results confirm that yield of transbronchial biopsy is determined by the type of tumor-bronchus relationship and the biopsy technique performed.

Palliative-radiotherapy in lumbosacral carcinomatous neuropathy.

The authors report their own experience in obtaining pain relief in 13 recurrent or disseminated cancer patients affected by lumbosacral carcinomatous neuropathy (LCN). The site, where the disease involved the lumbosacral plexus or its branches, was palliatively irradiated with a few large fractions. The average duration of response was 196 days. Median survival (uncensored) was 185 days (range 47-636 days).

Small bronchogenic carcinomas presenting as solitary pulmonary nodules. Bioptic approach guided by CT-positive bronchus sign.

To evaluate the utility of the CT bronchus sign in making a choice between transbronchial biopsy (TBB) and transthoracic needle aspiration (TTNA) as the first diagnostic procedure in a patient with a solitary pulmonary nodule (SPN), we reviewed the results of TBB and TTNA in 26 patients who had a bronchogenic carcinoma less than 3 cm, studied with thin-section CT. The patients were divided into two groups. Group 1 included ten cases with a third- to fifth-order bronchus sign. Group 2 included two cases with a sixth-order bronchus sign and 14 cases with absence of a bronchus sign. TBB was performed in all the patients; conversely, TTNA was carried out in 22 patients. In group 1, TBB gave a diagnostic yield in eight (80 percent) of ten patients, while TTNA was positive in three (42 percent) of seven patients (p > 0.05). Conversely, in group 2, results of TBB were normal in all the patients, while TTNA gave a diagnosis in 10 (66 percent) of 15 patients (p < 0.05). We think that TBB should be considered the method of choice in diagnosing SPNs associated with a third- to fifth-order bronchus sign; conversely, TTNA is more useful than TBB in diagnosing SPNs in the presence of a more peripheral bronchus sign or with the absence of a bronchus sign. In conclusion, we suggest routine evaluation with thin-section CT of each SPN to optimize diagnostic management.

Unusual relapse of hepatocellular carcinoma.

The authors report a patient with iatrogenic dissemination of hepatocellular carcinoma (HCC). A 65-year-old Caucasian man was found to have a moderately well-differentiated HCC diagnosed by laparoscopy and biopsy; the patient had atypical left liver lobe resection. Thirty-three months after definitive surgery a double relapse was found at the site of the previous laparoscopy and at the surgical scar; no other metastases were found. Surgical procedure for removal of these lesions was performed, and the patient received complementary radiation therapy. At 30 months of follow-up, the patient is alive and disease free. The risk of neoplastic seeding through biopsy and improved safety in surgical techniques justify the omission of diagnostic biopsy in patients who have surgical procedures.

[Contribution of computerized tomography to the diagnosis of patients with non-calcified solitary pulmonary nodule, without known neoplasm]. / Contributo della tomografia computerizzata alla diagnostica dei pazienti con nodulo solitario polmonare non calcifico, in assenza di neoplasia nota.

We define a solitary pulmonary noncalcified nodule (NPS) as a single focal rounded or ovoid lesion in the lung parenchyma, less than 4 cm in diameter, without associated adenopathy, atelectasis or pneumonia. An NPS, in the absence of a known primary malignancy, can be lung cancer (NPSM), a metastasis of unknown origin (NPSMT), or a benign lesion (NPSB). The best approach to the management of NPS and the value of CT are still controversial and uncertain. The finding on cross-section CT of a bronchus leading directly to, or contained within, the nodule is called "positive CT bronchus sign" (CT-BS). Our study was aimed at investigating the usefulness of CT bronchus sign, as studied on thin-slice (2 mm thick) CT sections, in order to establish the most appropriate diagnostic sequence in patients with solitary noncalcified pulmonary nodules (NPS). We evaluated 47 NPS (9 NPSB, 34 NPSM and 4 NPSMT) with thin-slice CT to detect the presence of CT bronchus sign. Seventeen cases had CT-BS (15 NPSM; 1 NPSB; 1 NPSMT); of them, 13 were diagnosed by means of transbronchial biopsy and brushing (TBB). Only one case (NPSM) of the 30 (19 NPSM; 3 NPSMT; 8 NPSB) without CT-BS, was diagnosed by TBB. TBB was negative in the 9 NPSB. The CT-BS is not pathognomonic of malignancy; in fact, the sign was observed in NPSB (one tuberculoma) too. Our results suggest that the CT bronchus sign is valuable in predicting the success of TBB in malignant solitary pulmonary nodules. On the other hand, it seems to be useless for NPSB. Therefore, to establish the most appropriate diagnostic sequence, thin-section CT should be performed in each patient with peripheral noncalcified lung lesions to plan whether TBB or transthoracic needle aspiration should come next. If biopsy results are poor, either surgery or the "wait and watch for growth" approaches can be suggested. The choice can be guided by the presence of predisposing factors for cancer or infection.

Bronchus sign on CT in peripheral carcinoma of the lung: value in predicting results of transbronchial biopsy.

The bronchus sign on CT represents the presence of a bronchus leading directly to a peripheral pulmonary lesion. We investigated the value of this sign in predicting the results of transbronchial biopsy and brushing in 33 consecutive cases of proved peripheral bronchogenic carcinoma studied with thin-slice CT (2-mm-thick sections). The bronchus sign was seen on CT in 22 patients and was absent in 11. Transbronchial biopsy and brushing showed peripheral carcinoma in 13 (59%) of 22 patients in whom the bronchus sign was seen on CT and in only two (18%) of 11 patients in whom it was not seen. The difference is statistically significant (Fisher's exact test, p = .029). When analyzed by the order of involved bronchus, a 90% success rate of transbronchial biopsy and brushing was found in patients in whom the bronchus sign was seen at a fourth-order bronchus (p = .01). This compared with a success of 33% when the bronchus sign was seen at fifth-, sixth-, or seventh-order branches. Our results suggest that the bronchus sign at a fourth-order bronchus is valuable in predicting the success of transbronchial biopsy and brushing. The presence of the sign on CT may be useful in determining if the workup should include transbronchial biopsy and brushing or transthoracic needle aspiration in patients with peripheral lung lesions.

[Conservative treatment of early breast carcinoma. Localization of the booster field]. / Trattamento conservativo del carcinoma mammario iniziale. Localizzazione del volume bersaglio da sovradosare.

The definition of the methods for localizing the booster field used in the conservative treatment of early breast cancer is often blurred in several studies in the current literature. This paper is aimed at reporting a surgical-radiological method more objective than the clinico-anamnestic one used, so far, for planning the booster field. To this purpose 33 patients underwent conservative surgery in healthy tissue and radiopaque clips were inserted at the margins of the excision cavity. The booster field as defined with clinico-anamnestic standards was then simulated and later verified by a radiation therapy simulator. The clinical fields thus set up were correct in 15/33 cases. The authors discuss their results and compare them with literature data. The importance of the use of the surgical-radiological method to localize the booster field is stressed.

[Clodronate and radiotherapy for the treatment of osteolysis caused by metastasis of breast carcinoma and non-small cell lung carcinoma. A retrospective study]. / Clodronato più radioterapia nel trattamento delle osteolisi metastatiche da carcinoma mammario e polmonare non microcitoma. Studio retrospettivo.

We have retrospectively examined 94 evaluable patients with metastatic osteolysis from breast cancer (BC) and non-small cell lung (NSCLC) cancer, who received RT from Nov. 88 to Nov. 89.27 (15 BC and 12 NSCLC) were in treatment with Clodronate for at least 3 days from the beginning of RT; of the remaining 67 treated with RT alone, 31 had NSCLC and 36 BC. We have evaluated: increase in pain (IP) occurring on the first days of RT, percentages of complete pain relief (CPR) at the end of RT and 4-6 weeks after. A decreased occurrence of IP was observed more in NSCLC patients receiving RT + Clodronate compared to those treated with RT alone (33.3% vs 41.9%). Both at the end of RT and 4-6 weeks after, we registered a significant difference in the percentages of CPR in the RT + Clodronate group (40.7 vs 20.9 and 70.3% vs 53.7%). We believe the points of interest focused in this paper-greater precision in centering and defining the target volume, decreased occurrence of IP during the first days of RT, increase in percentage of CPR--need a prospective confirmation.