Malignant respiratory-digestive fistulas.

PURPOSE OF REVIEW: Malignant tracheoesophageal or bronchoesophageal or, less commonly, esophageal-lung parenchyma fistulas are late developments of advanced cancer of the esophagus, lung or mediastinum. Patients present mainly with intractable cough and repeated respiratory infections. Rapid deterioration and death results if this condition is left untreated. RECENT FINDINGS: The use of the antiangiogenesis drug bevacizumab along with radiation therapy have been linked to the development of malignant tracheoesophageal fistula/malignant bronchoesophageal fistula in patients treated for both small-cell and nonsmall-cell lung carcinoma. Three case series have been published during 2009 presenting characteristics, treatment options and associated complications. The best palliation for this malignant condition is achieved with endoscopic placement of esophageal, respiratory or parallel stenting (esophagus and airway). Dual stenting appears to work better than single prosthesis both for palliation and safety. There were also some reports of unusual complications related to prosthesis placement as treatment of this condition. Particular attention has to be paid to tracheal compression/erosion secondary to esophageal stents. SUMMARY: Respiratory-digestive fistulas are devastating complications of advanced cancer. Research has brought new understanding relevant to clinical practice.

[Clinical trials that have changed our practices 2010-2020]. / Les essais cliniques en radiothérapie qui ont changé les pratiques 2010­2020.

PURPOSE: This article aims to describe and list the clinical trials that have changed our practices in breast cancer, urological cancer, gynecological cancer, cancer of the upper aerodigestive tract and digestive cancer in the last ten years. MATERIAL AND METHODS: We listed and selected the studies published between 2010 and 2020. The articles were identified on the basis of a Medline search with PubMed and knowledge of the authors. RESULTS: Five to six trials were selected in breast cancer, urological cancers, gynecological cancers, cancers of the upper aerodigestive tract and digestive cancers asking the different fundamental questions in radiotherapy. CONCLUSION: Depending on the pathologies, the questions raised over the past 10 years remain fundamental questions such as the place of neoadjuvant treatment, the place of hypofractionation or the type of chemotherapy concomitant with radiotherapy.

Polymorphic reticulosis limited to the upper aerodigestive tract--natural history and radiotherapeutic considerations.

Polymorphic reticulosis (PMR) is a specific clinicopathological entity which commonly presents as an aggressive, necrotizing lesion of the upper airway. It is a separate nosologic entity from Wegener's granulomatosis, though its site and aggressive nature has lead to confusion in the distinction between these two different processes. Although radiotherapy has been acknowledged as the treatment of choice for limited upper airway PMR, little data exist to guide the radiation oncologist in the practical management of this disorder. We review our single institutional experience with PMR limited to the upper airway. Thirty-four patients (24 males, 10 females) with a median age of 44 years (range 19-80 years) are presented. Symptoms of nasal obstruction were present in 94%. Systemic symptoms such as fever, night sweats, and weight loss were noted in 62% and were often striking clinically. The nasal mucosa was most frequently involved (91%), although involvement of the paranasal sinuses (47%), palate (32%), as well as, other upper airway sites was not uncommon. Perforation of involved structures was recorded in 37%. All but 1 patient were treated with primary radiotherapy. Twelve relapsed with PMR and 3 additional patients manifested diffuse histiocytic lymphoma either within or adjacent to the original treatment field. The median survival relapse in these 15 patients was only 4 months, although 25% were salvaged at 5 years post-relapse. The overwhelming majority of relapses were noted within the first 3 years following treatment. An evaluation of radiotherapy parameters indicated that a minimum dose of 42 Gy or a TDF of 70 is necessary to achieve long-term local control. Pattern of failure analysis demonstrated in-field failure as the predominant failure site, and this problem should become much less significant with implementation of proper time-dose-fractionation schemes. Marginal failure was noted in 20% as a component of eventual failure sites suggesting the need for generous treatment volumes including clinically uninvolved adjacent structures at risk, such as palate, sinuses, and nasopharynx for nasal lesions. Finally, systemic failure occurred in 25%. Although this rate may be reduced by improved local treatment measures, ultimately effective systemic chemotherapy will be required to substantially impact on these patients' survival.

Lhermitte's sign: incidence and treatment variables influencing risk after irradiation of the cervical spinal cord.

PURPOSE: Lhermitte's sign is a relatively infrequent sequela of irradiation of the cervical spinal cord. In this study, we sought to determine whether various treatment parameters influenced the likelihood of developing Lhermitte's sign. METHODS AND MATERIALS: Between October 1964 and December 1987, 2901 patients with malignancies of the upper respiratory tract were treated at the University of Florida. The dose of radiation to the cervical spinal cord was calculated for those patients who had a minimum 1-year follow-up. A total of 1112 patients who received a minimum of 3000 cGy to at least 2 cm of cervical spinal cord were included in this analysis. RESULTS: Forty patients (3.6%) developed Lhermitte's sign. The mean time to development of Lhermitte's sign after irradiation was 3 months, and the mean duration of symptoms was 6 months. No patient with Lhermitte's sign developed transverse myelitis. Several variables were examined in a univariate analysis, including total dose to the cervical spinal cord, length of cervical spinal cord irradiated, dose per fraction, continuous-course compared with split-course radiotherapy, and once-daily compared with twice-daily irradiation. Only two variables proved to be significant. Six (8%) of 75 patients who received > or = 5000 cGy to the cervical spinal cord developed Lhermitte's sign compared with 34 (3.3%) of 1037 patients who received < 5000 cGy (p = .04). For patients treated with once-daily fractionation, 28 (3.4%) of 821 patients who received < 200 cGy per fraction developed Lhermitte's sign compared with 6 (10%) of 58 patients who received > or = 200 cGy (p = .02). CONCLUSION: An increased risk of developing Lhermitte's sign was demonstrated for patients who received either > or = 200 cGy per fraction (one fraction per day) or > or = 5000 cGy total dose to the cervical spinal cord.

Modulation of dose intensity in aerodigestive tract cancers: strategies to reduce toxicity.

Advances in diagnostic and therapeutic radiology and a better understanding of cell biology are being applied in practical ways to modulate treatment morbidity. Conformal radiotherapy targets the cancer precisely and can be combined with new systemically administered radiosensitizers. The successes of conventional chemoradiation programs support continued study of newer ways to deliver systemic radiosensitizing chemotherapy. However, chemoradiation creates a narrower therapeutic window compared to irradiation alone and increased treatment intensity, even with conformal chemoradiation techniques, can potentially result in frequent complications, detrimental treatment delays, and decreased quality of life. Treatment schedules employing a "best tolerated time" modelfor systemic administration of radiosensitizing chemotherapy, based on the concept of chronotolerance, offer attractive ways to address the challenging problem of normal tissue toxicity associated with conformal chemoradiation. This approach may be beneficial in the elderly and those medically unfit to tolerate traditional dose-intense combined-modality schedules. Further evaluation of this concept is warranted, based on existing data.

Kinetics of tumor growth and of cell proliferation in U.R.D.T. cancers: therapeutic implications.

After a brief survey of the factors of clinical tumor radioresistance the available data on the growth rate and on the kinetics of cell proliferation of U.R.D.T. tumors are reviewed. The growth fraction and the cell turnover rate appear to be similar in U.R.D.T. tumors and in other squamous cell carcinomas. These two parameters are correlated with clinical tumor radiosensitivity and chemosensitivity. The possible value of tailoring fractionation and drug administration to the biological characteristics of the tumor is discussed.

Intraoperative radiation therapy in the multimodality approach to upper aerodigestive tract cancer.

The cure rate of operable lung cancer and locally advanced head and neck cancer remains suboptimal, with a limited rate of local control despite improvements in the surgical removal of primary tumors and in methods for mediastinal lymph node dissection, in particular. The efficacy of adjuvant therapy, such as EBRT, has improved, and the immediate efficacy of new chemotherapeutic drugs is increasingly significant, although local recurrences remain frequent. Locoregional failure is not uncommon in upper aerodigestive tract cancers. Factors limiting radiocurability for locally advanced (stage III) lung cancer include mediastinal intolerance of irradiation (high risk of mediastinal fibrosis, which increases exponentially when levels of much more than 50 Gy are administered to the whole mediastinum) and the very high radiosensitivity of the healthy lung, which can develop fibrosis with relatively small or moderate doses starting at 18 to 20 Gy, and even more frequently when larger volumes are irradiated. Head and neck neoplasms are less difficult sites in which to administer doses of up to 70 Gy of external beam radiotherapy initially, but, like locoregionally recurrent lung cancers, they are not easily reirradiated with tumoricidal doses of EBRT. For these reasons, IORT seems to be a good option for increasing local control, because areas of [figure: see text] residual microscopic disease may be irradiated using IOERT approaches without affecting critical organs to the same extent. In addition, careful patient selection is paramount. Combined modality treatment regimens incorporating IORT may benefit patients with locally advanced disease. The ability of IORT to sterilize microscopic residual disease can enhance the "completeness" of resection and thus, theoretically, improve local control. Although distant disease dissemination remains by far the overriding issue, as newer effective agents emerge, local failure will continue to be a problem. Preliminary studies have demonstrated that IORT can be administered to patients who have locally advanced NSCLC and head and neck cancer, in the context of aggressive combined modality therapy, and is generally well tolerated. Long-term efficacy and benefit can only be determined in the setting of carefully designed clinical trials. (See the article by Thomas and Merrick elsewhere in this issue for further discussion of this topic.) Several relatively small, single-institution pilot studies exploring the utility and benefit of IORT for locally advanced upper aerodigestive tract cancers have been conducted. Clear conclusions have been difficult to determine because of the mixing of disease stages, varying degrees and completeness of surgical resection, varying radiation doses, different schemas, and other factors. Yet, given the major morbidity and mortality associated with locally recurrent lung cancer, methods of improving local control need to be pursued and refined. Encouraging preliminary data suggest that IOERT can be safely administered and may benefit local control. Based on several centers' expertise in the combined modality treatment of locally advanced lung cancer and familiarity with IORT, the UCSF Thoracic Oncology Program has proposed a multicenter phase 2 study incorporating IORT in a combined multimodality treatment schema for patients who have completely resected locally advanced stage IIIA and IIIB NSCLC (nonpleural effusion, non-N3) (Fig. 1). It is hoped that this study will commence in the upcoming year.

Whole-lung irradiation for Kaposi's sarcoma.

Twenty-five patients were treated with whole-lung irradiation for symptomatic pulmonary KS. Treatment was most often given four days per week, 150 cGy per fraction, to 1050-1500 cGy (mean 1224 cGy). No acute toxicity was observed. 89% of patients completing therapy reported improvement in dyspnea. All patients responding symptomatically could reduce (and 78% could eliminate) oxygen use. Chest x-rays showed concurrent improvement in 78% of cases, although this was > or = 50% clearance of infiltrate in only 28%. Symptomatic improvement was prompt, always occurring during the 2-2 1/2 week therapy course. Clinical response was transient in some patients, but 12 weeks after therapy 56% remained symptomatically improved. Pulmonary KS indicated an advanced stage of AIDS and survival was short (mean: 15.7 weeks after completion of therapy). Patients with poor performance status (Karnovsky: < or = 30%) and progression of disease despite chemotherapy had very short survival (mean: 3.2 weeks). For such patients, a supportive care only approach without radiotherapy is suggested. For others, whole-lung irradiation provides prompt symptomatic improvement for most patients, and offers a simple treatment approach with little toxicity for often debilitated patients.

[Chemotherapy of carcinoma of the upper respiratory and digestive tract]. / Chimiothérapie des carcinomes des voies aéro-digestives supérieures.

New regimens of chemotherapy in previously untreated squamous cell head and neck carcinoma yielded a 60 per cent rate of regression in over 50 per cent of patients. Planned radical surgery may be delayed and curative irradiation is often preferred. However, many patients have been excluded for polychemotherapy because of poor general condition. The results of simultaneous perioperative chemotherapy and X-ray therapy are not well known. Adjuvant chemotherapy after initial treatment is difficult to apply and to appreciate for results. Chemotherapy of recurrences is disappointing, even if efficient. Randomised trials are necessary to improve our knowledge in this field.

[Changes in the serum protein profile during radiotherapy of the upper respiratory and digestive tracts]. / Evolution du profil protéique sérique au cours de la radiothérapie des voies aéro-digestives supérieures.

Patients with a cancer of the upper airways or upper gastro-intestinal tract present a state of malnutrition as a result of the disease itself and, more importantly, as a result of its localisation. Loco-regional radiotherapy often leads to an aggravation of this state. The protein profile, consisting of nine serum proteins, was determined each week in 54 patients with cancer of the upper respirato-gastro-intestinal tract receiving radiotherapy. During the course of radiotherapy, the already altered nutritional state of these patients deteriorated further, as shown by a regular and significant downturn in the weight curve. The weekly monitoring of the protein profile showed a gradual and significant decrease in the levels of nutritional proteins (prealbumin, retinol binding protein, transferrin) and immunoglobulins (IgM, IgA) and a small variation in the levels of inflammatory proteins (haptoglobin, orosomucoid, C3 complement fraction, alpha 1-antitrypsin). The protein profile, established on the basis of carefully selected proteins, can provide useful information in the monitoring of a patient's nutritional state.

[Accelerated radiotherapy: initial results in a series of locally very advanced carcinomas of the upper respiratory and digestive tracts]. / Radiothérapie accélérée: premiers résultats dans une série de carcinomes des voies aéro-digestives supérieures localement très évolués.

From 1992 to 1993, 46 patients with very locally advanced (74% T4) head and neck carcinomas and extensive cervical involvement (82% N2-3) were treated at the Institute Gustave Roussy with a very accelerated radiotherapy regimen: 62 Gy in three weeks with two daily 1.75 Gy fractions. Early mucosal reactions were severe but manageable in this population of patients with frequent alteration of initial performance status. Nearly every patient experienced a grade 3 or 4 (WHO) mucositis and 80% required tube feeding. Follow-up is not sufficient to draw firm conclusion about late reactions but they do not seem different from those induced by conventional radiotherapy. The overall 2-year survival rate of 49.4% and loco-regional control rate of 67% seem superior to the results of conventional radiotherapy for such advanced tumors. These results have led to a multi-center randomized controlled trial comparing this regimen of accelerated radiotherapy with conventional fractionated radiotherapy.

[Surgical, radiation and combined treatment of multiple primary malignancies of the respiratory system]. / Khirurgicheskoe, kombinirovannoe i luchevoe lechenie pervichno-mnozhestvennykh zlokachestvennykh opukholei organov dykhaniia.

Surgery for primary multiple malignant tumors of the respiratory system was carried out in 141 patients. Reconstruction, plastic operations and sparing resections were performed in 79 cases (68.5%). Five-year survival after radical surgery was 43.8%.

[The use of clindamycin and netilmicin for preventing postoperative wound infection in patients with cancer of the upper respiratory and digestive tracts]. / Primenenie klindamitsina i netilmitsina dlia profilaktiki posleoperatsionnoi ranevoi infektsii u bol'nykh rakom verkhnikh dykhatel'nykh i pishchevaritel'nykh putei.

Clindamycin (2.7 g/day) and netilmicin (5.6 mg/kg) were used for 6-10 days in 27 patients with laryngeal and oral cancer versus beta-lactam antibiotics and aminoglycosides received by 56 matched patients to prevent infection of the operative wound. Suppuration was observed in 11.1 and 41.4% of the patients, respectively (p < 0.05), the temperature rose over 38 degrees C in 22.2% and 42.9% of the patients, respectively (p < 0.05). The regimens showed similar toxicity. The findings proved high efficacy of clindamycin combination with netilmicin in infection prophylaxis in patients operated on for upper respiratory and digestive tract cancer.

Dosimetry of a small air cavity for clinical electron beams: A Monte Carlo study.

This study investigated dosimetric changes in a water phantom when a small air cavity was presented at the central axis of a clinical electron beam. We used 6-, 9-, and 16-MeV electron beams with a 10 x 10 cm(2) applicator and cutout produced by a Varian 21 EX linear accelerator. Percentage depth doses (PDDs) for different depths (0.5-7 cm), thicknesses (2-10 mm), and widths (1-5 cm) of air cavities were calculated using Monte Carlo simulations (EGSnrc code) validated by film measurements. By comparing PDDs of phantoms with and without the air cavity, it was found that when the depth or thickness of cavity was changed, the PDD curve below the cavity was shifted with a distance equal to the thickness of the cavity. However, when the width of the air cavity was changed, both the PDD curve and its slope within and below the cavity were changed. A larger width of the air cavity resulted in a shallower PDD curve within the cavity. The slope of the PDD curve below the cavity tended towards a value as the width of the air cavity was increased to 3-5 cm for the 6-, 9-, and 16-MeV electron beams. The dependence of the depth dose on the width of the air cavity is a result of the contribution of the electron side scattering in the water surrounding the cavity. The change in depth dose resulting from the presence of an air cavity can cause discrepancies between the calculated and actual dose during radiotherapy, unless the effects of the air cavity are properly characterized during treatment planning. From the dosimetry data in this study, neglecting an air cavity of 1-cm thickness in the build-up region of a 6-MeV electron beam resulted in a delivered dose 10-12% larger than the original prescription. Delivered doses 3% and 6% higher than the prescribed dose were observed when doses were prescribed at R(80) for a 16-MeV electron beam. These results were obtained by neglecting air cavities with thicknesses equal to 2 and 4 mm, respectively, at a depth of 5 cm.