Impact of image-guided radiotherapy to reduce laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers

We would like to determine the effectiveness of image-guided radiotherapy (IGRT) to reduce laryngeal edema following treatment for head and neck cancer and to assess patient perception of voice and speech after treatment. We conducted a retrospective review of 44 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Endoscopic and/or mirror examinations of the larynx were performed following radiotherapy at each follow-up visit. Laryngeal edema was assessed based on the Radiation Therapy Oncology Group grading scale. Patients were also asked to rate about the voice and speech quality relative to their pre-radiotherapy status. The mean laryngeal dose was 16.3 Gy (range: 11.7–45.5 Gy). At a median follow-up of 14 months (range: 2–31 months), three patients (7%) developed laryngeal edema (one grade 1, two grade 2). The mean laryngeal dose was respectively 20.3 Gy in two patients and 20.7 Gy in the third patient developing laryngeal edema. Except for one patient who continued to smoke and drink after radiotherapy, no patient reported any significant change in voice and speech quality after treatment. IGRT results in low rates and low severity of laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers and may preserve voice quality.     

Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma--the University of Iowa experience

PURPOSE: To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma. METHODS AND MATERIALS: From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis. Of the remaining 150 patients, 99 were treated with definitive IMRT, and 51 received postoperative IMRT. Sites included were nasopharynx, 5; oropharynx, 56; larynx, 33; oral cavity, 29; hypopharynx, 8; nasal cavity/paranasal sinus, 8; and unknown primary, 11. None of the patients treated with postoperative IMRT received chemotherapy. Of 99 patients who had definitive IMRT, 68 patients received concurrent cisplatin-based chemotherapy. One patient received induction cisplatin-based chemotherapy, but no concurrent chemotherapy was given. Three clinical target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 in the definitive cohort were 70-74 Gy, 60 Gy, and 54 Gy, respectively. For high-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 64-66 Gy, 60 Gy, and 54 Gy, respectively. For intermediate-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 60 Gy, 60 Gy, and 54 Gy. RESULTS: The median follow-up was 18 months (range, 2-60 months). All living patients were followed for at least 6 months. There were 11 local-regional failures: 7 local failures, 3 regional failures, and 1 failure both in the primary tumor and regional lymph node. There were 16 patients who failed distantly, either with distant metastasis or new lung primaries. The 2-year overall survival, local progression-free survival, locoregional progression-free survival, and distant disease-free survival rates were 85%, 94%, 92%, and 87%, respectively. The median time from treatment completion to local-regional recurrence was 4.7 months (range, 1.8 to 15.6 months). Only one marginal failure was noted in a patient who had extensive tonsil cancer with tumor extension into the orbit and cavernous sinus. Patients with oropharyngeal cancer did significantly better than patients with oral cavity and laryngeal cancer, with a 2-year local-regional control rate of 98%, compared with 78% for oral cavity cancer and 85% for laryngeal cancer (p = 0.005). There was no significant difference in local-regional control for patients who received postoperative radiation or definitive radiation (p = 0.339) and for patients who had chemotherapy or not (p = 0.402). Neither T stage nor N stage had a significant effect on local-regional control (p = 0.722 and 0.712, respectively). CONCLUSIONS: Our results have confirmed the effectiveness of IMRT in head-and-neck cancer. It offers excellent outcomes in local-regional control and overall survival. More studies are necessary to further improve the outcomes of laryngeal cancer as well as oral cavity cancer.     

Dosimetric predictors of xerostomia for head-and-neck cancer patients treated with the smart (simultaneous modulated accelerated radiation therapy) boost technique

PURPOSE: To evaluate the predictors of xerostomia in the treatment of head-and-neck cancers treated with intensity-modulated radiation therapy (IMRT), using the simultaneous modulated accelerated radiation therapy (SMART) boost technique. Dosimetric parameters of the parotid glands are correlated to subjective salivary gland function. MATERIALS AND METHODS: Between January 1996 and June 2000, 30 patients with at least 6 months follow-up were evaluated for subjective xerostomia after being treated definitively for head-and-neck cancer with the SMART boost technique. Threshold limits for the ipsilateral and contralateral parotid glands were 35 Gy and 25 Gy, respectively. Dosimetric parameters to the parotid glands were evaluated. The median follow-up time was 38.5 months (mean 39.9 months). The results of the dosimetric parameters and questionnaire were statistically correlated. RESULTS: Xerostomia was assessed with a 10-question subjective salivary gland function questionnaire. The salivary gland function questionnaire (questions 1, 2, 3, 4, 6, and 9) correlated significantly with the dosimetric parameters (mean and maximum doses and volume and percent above tolerance) of the parotid glands. These questions related to overall comfort, eating, and abnormal taste. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. CONCLUSIONS: Questions regarding overall comfort, eating, and abnormal taste correlated significantly with the dosimetric parameters of the parotid glands. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. Dosimetric sparing of the parotid glands improved subjective xerostomia. IMRT in the treatment of head-and-neck cancer can be exploited to preserve the parotid glands and decrease xerostomia. This is feasible even with an accelerated treatment regimen like the SMART boost. More patients need to be evaluated using IMRT to identify relevant dosimetric parameters.     

Radiation therapy for squamous cell carcinoma of the esophagus

Between 1965 and 1981, 119 patients with squamous cell carcinoma of the esophagus were treated with radiation therapy with curative intent. Radiation was employed in combination with surgery and delivered pre- and/or postoperatively in 20 patients (17%). The remainder received radiotherapy alone. The overall survival rate was statistically higher in patients who had surgery and radiation compared to the group receiving radiation alone. The one-, two-, and five-year survival rates of patients receiving combined treatment vs radiotherapy alone were 65% vs 35%, 25% vs 14%, and 15% vs 6%. Age, total radiation dose, and inclusion of the supraclavicular areas in the radiation portals did not impact on outcome. Other prognostic factors are discussed. Long term survivors were noted to be at substantial risk for the development of a second epidermoid malignancy in the upper aerodigestive tract. Cumulative risk at five years was approximately 25%.     

Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT?

PURPOSE: To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT. METHODS AND MATERIALS: A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer. RESULTS: The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p < 0.001), and, similarly, the glottic larynx. The constrictors and the glottic and supraglottic larynx were, therefore, deemed the DARS. The lowest maximal dose delivered to a stricture volume was 50 Gy. Reducing the volumes of the DARS receiving > or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose. CONCLUSIONS: The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.     

Endoluminal and Interstitial Brachytherapy for the Treatment of Gastrointestinal Malignancies: a Systematic Review

Radiation therapy is an integral component in the multimodality management of many gastrointestinal (GI) cancers at all stages of clinical presentation. With recent advances in technology and radiation delivery, external beam radiation therapy (EBRT) can be delivered with reduced toxicity. However, despite these advances, EBRT doses are still limited by the presence of radiosensitive serial structures near clinical targets in the GI tract. Relative to EBRT techniques, brachytherapy techniques have a lower integral dose and more rapid fall-off, allowing for high-dose delivery with little normal tissue exposure. Given the unique characteristics of brachytherapy, it is an attractive strategy to treat GI malignancies. This review addresses the application of both high-dose rate brachytherapy (HDRBT) and low-dose rate brachytherapy (LDRBT) to multiple GI malignancies for both definitive and palliative management.     

Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer

BACKGROUND: A significant portion of head-and-neck cancer patients will develop persistent or recurrent disease after definitive treatment. Radiation therapy is often used as definitive therapy or as an adjunct to surgery. Recurrent cancer of the head and neck in the previously irradiated field is, thus, a common occurrence and poses a therapeutic challenge. Some studies have evaluated low-dose-rate (LDR) brachytherapy as a therapeutic option, including a large case series with long-term follow-up by our own institution. High-dose-rate (HDR) brachytherapy offers therapeutic advantages over LDR brachytherapy. This study evaluates the local control and outcomes of patients with previously irradiated recurrent head-and-neck cancer treated with HDR interstitial brachytherapy. METHODS AND MATERIALS: Between 1997 and 2002, 30 patients who received prior radiation therapy for primary tumors of the head and neck were treated for biopsy-proven recurrent disease. All patients received previous radiation as definitive therapy alone or as adjunct to surgery. All patients were inoperable, refused surgery, or had gross residual disease after salvage surgery for their recurrent disease. Thirty-six sites on the 30 patients were implanted by application of high-dose-rate interstitial brachytherapy techniques with mean tumor dose of 34 Gy (18-48 Gy) in twice daily fractions of 300 to 400 cGy per fraction. RESULTS: At a minimum follow-up of 12 months, local tumor control was achieved in 69% of implanted sites. Disease-specific survival at 1 and 2 years was 54% and 45%, respectively. Overall survival at 1 and 2 years was 56% and 37%, respectively. Grade 3/4 late complications occurred in 16% of the patients. No fatal complications occurred. CONCLUSION: HDR brachytherapy can play an important role in the salvage treatment of previously irradiated recurrent head-and-neck cancer. This study shows that comparable results are obtained by HDR brachytherapy with fewer late complications than were indicated by previously reported data for LDR brachytherapy.     

Contribution of radiation biology to the development of radiation therapy]

Results of radiation therapy for malignant tumors have steadily improved, and both radiation biology and radiation physics have contributed to this improvement. As examples of such contribution, radiobiologically-elaborated continuous hyperfractionated accelerated radiotherapy (CHART) has been proven to be superior to conventional radiotherapy against non-small cell lung cancer, and a hypoxic cell sensitizer nimorazole has been proven to be effective against pharyngeal and supraglottic laryngeal cancers. Based on laboratory studies, a combination of chemotherapy and radiotherapy has been shown to be superior to radiotherapy alone in many cancers. Radiation biology has also provided important fundamental data for clinical applications of heavy ion and proton beam therapy. In the future, useful predictive assays and radioprotectors are also expected to be developed. Radiation biology should continue to contribute to the further development of clinical radiation therapy.     

A Review of Immunotherapy for Stage III and Metastatic Non-Small Cell Lung Cancer and the Rationale for the ECOG-ACRIN EA5181 Study

ECOG‐ACRIN EA5181 is a phase III prospective, randomized trial that randomizes patients undergoing chemo/radiation for locally advanced non‐small cell lung cancer (LA‐NSCLC) to concomitant durvalumab or no additional therapy, with both arms receiving 1 year of consolidative durvalumab. Radiation dose escalation failed to improve overall survival in RTOG 0617. However, conventionally fractionated radiation to 60 Gy with concomitant chemotherapy is associated with a high risk of local failure (38%–46%). It is hoped that concomitant immunotherapy during chemo/radiation can help decrease the risk of local failure, thereby improving overall survival and progression‐free survival with acceptable toxicity. In this article, we review conventional chemo/radiation therapy for LA‐NSCLC, as well as the quickly evolving world of immunotherapy in the treatment of non‐small cell lung cancer and discuss the rationale and study design of EA5181.Implications for PracticeThis article provides an up‐to‐date assessment of how immunotherapy is reshaping the landscape of metastatic non‐small cell lung cancer (NSCLC) and how the impact of this therapy is now rapidly moving into the treatment of patients with locally advanced NSCLC who are presenting for curative treatment. This article reviews the recent publications of chemo/radiation as well as those combining immunotherapy with chemotherapy and chemo/radiation, and provides a strategy for improving overall survival of patients with locally advanced NSCLC by using concomitant immunotherapy with standard concurrent chemo/radiation.     

Surgical Salvage of Recurrent Cancer of the Head and Neck

The therapeutic options and prognosis for recurrent squamous cell carcinoma of the upper aerodigestive tract vary greatly depending on site, extent of disease, and previous treatment. Surgical salvage represents the primary curative option when recurrent disease is resectable. Common factors associated with poor salvage surgery outcomes include positive surgical margins, lack of disease-free interval following previous definitive radiation therapy, advanced initial and recurrent tumor stage, and presence of concomitant recurrent neck disease. Surgical salvage of oropharyngeal and hypopharyngeal recurrences after primary chemoradiation therapy is associated with significant patient morbidity and poor long-term survival. Patients with laryngeal recurrences generally have the best comparative survival and functional outcomes, while patients with oral cavity recurrences have a relatively intermediate prognosis. Nasopharyngeal recurrences have often been treated with reirradiation, but surgical salvage represents the best option for small recurrences confined to the nasopharynx. Most patients with recurrent upper aerodigestive tract squamous cell carcinoma after previous aggressive therapy are not curable, and clinical judgment in determining which patients are appropriate candidates for salvage surgery is paramount.     

Treatment failure prediction for head-and-neck cancer radiation therapy

PurposeTreatment outcome prediction is an important emerging topic in oncologic care. To support radiation oncologists on their decisions, with individualized, tailored treatment regimens increasingly becoming the standard of care, accurate tools to predict tumour response to treatment are needed. The goal of this work is to identify the most determinant factor(s) for treatment response aiming to develop prediction models that robustly estimate tumour response to radiation therapy in patients with head-and-neck cancer.Patients and methodsA population-based cohort study was performed on 92 patients with head-and-neck cancer treated with radiation from 2007 until 2014 at the Portuguese Institute of Oncology of Coimbra (IPOCFG). Correlation analysis and multivariate binary logistic regression analysis were conducted in order to explore the predictive power of the considered predictors. Performance of the models is expressed as the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. A nomogram to predict treatment failure was developed.ResultsSignificant prognostic factors for treatment failure, after multivariate regression, were older age, non-concomitant radiation therapy and larger primary tumour volume. A regression model with these predictors revealed an AUC of .78 for an independent data set.ConclusionFor patients with head-and-neck cancer treated with definitive radiation, we have developed a prediction nomogram based on models that presented good discriminative ability in making predictions of tumour response to treatment. The probability of treatment failure is higher for older patients with larger tumours treated with non-concomitant radiation.     

How to reduce radiation-related toxicity in patients with cancer of the head and neck

Radiation for head and neck cancers is often curative, but high doses are used. Normal tissues, including mucosa, salivary glands, and muscles, are exposed to these high doses, resulting in severe mucositis, xerostomia, and dysphagia. Efforts to minimize toxicity have involved advances in radiation physics and development of pharmacologic agents. Radiation techniques include conformal and intensity-modulated therapy, which minimizes dose to normal tissues while delivering high doses to tumor targets. Drugs used to prevent mucositis have targeted infection, but recently interest has been shown in the use of growth factors. Cholinergic agonists and cytoprotective agents, specifically amifostine, can address xerostomia. Involvement of speech pathologists in evaluation and treatment of patients with dysphagia can minimize swallowing difficulties and identify the tissues most responsible for swallowing. Minimizing radiation dose to these tissues may lower the incidence of radiation-induced dysphagia.     

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma

To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with head-and-neck cancer.

A panel consisting of members of the American Brachytherapy Society (ABS) performed a literature review, added information based upon their clinical experience, and formulated recommendations for head-and-neck HDR brachytherapy.

The ABS recommends the use of brachytherapy as a component of the treatment of head-and-neck tumors. However, the ABS recognizes that some radiation oncologists are reluctant to employ brachytherapy in the head-and-neck region because of the complexity of the postoperative management and concerns about radiation safety. In this regard, HDR eliminates unwanted radiation exposure and thereby permits unrestricted delivery of clinical care to these brachytherapy patients. The ABS made specific recommendations for previously untreated and recurrent head-and-neck cancer patients on patient selection criteria, implant techniques, target volume definition, and HDR treatment parameters (such as time, dose, and fractionation schedules). Suggestions were provided for treatment with HDR alone and in combination with external beam radiation therapy. It should be recognized that only limited experiences exist with HDR brachytherapy in patients with head-and-neck cancers. Therefore, some of these suggested doses have not been extensively tested in clinical practice. Hence, these guidelines will be updated as significant new outcome data are available. Any clinician following these guidelines is expected to use clinical judgment to determine an individual patient’s treatment.

Little has been published in the clinical literature on HDR brachytherapy in head-and-neck cancer. Based upon the available information and the clinical experience of the panel members, general and site-specific recommendations were offered. Areas for further investigations were identified.     

Salvage laryngectomy: oncological and functional outcome

The purpose of the research was to evaluate postoperative complications, functional outcome and survival after salvage laryngectomy. Second, to evaluate the management of the neck in combination with a laryngectomy in this group of patients. A retrospective analysis of all patients who underwent total laryngectomy for residual or recurrent squamous cell laryngeal carcinoma after (chemo)radiotherapy between November 1990 and June 2007 was performed. Of the 120 patients that were included, the complication rate was 56% (33% major and 23% minor). In univariate analyses, T-stage (p=0.05), bilateral neck dissection (p=0.09) and ASA score (p=0.08) showed a trend for postoperative major complications. Lymph node metastases were found in 26% of the neck dissection specimens, with a trend towards more regional disease at higher initial N-stage (p=0.06) and T-stage (p=0.08). Five-year disease specific survival was 58%. In univariate analyses pre-operative chemoradiation (vs. radiation) (p=0.0001), N3 neck (p=0.001) and positive surgical margins (p=0.02) were significant predictors for a worse disease specific survival, but only positive surgical margins (p<0.001) maintained significance in multivariate analysis. Eighty-seven percent of the patients were able to produce speech using a voice prosthesis, and 84% of the patients were able to have a 'normal' or 'soft' diet. There was an almost significant increase in mean body mass index (BMI) 6-12 months postoperative (p=0.057). Laryngectomy after radiotherapy offers good survival, with a substantial risk of complications and good functional outcome.     

Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma

PURPOSE: The treatment of malignant pleural mesothelioma remains a therapeutic challenge, with median survival rates of about 12 months and local failure rates of up to 80%. Our institution recently published results showing that extrapleural pneumonectomy (EPP) followed by hemithoracic radiation yielded excellent local control. This paper reports our technique for high-dose hemithoracic radiation after EPP. METHODS: Between 1990 and 2001, 35 patients with malignant pleural mesothelioma were treated with EPP followed by hemithoracic radiation therapy (median dose: 54 Gy, range: 45-54 Gy) at Memorial Sloan-Kettering Cancer Center. EPP was defined as en bloc resection of the entire pleura, lung, and diaphragm with or without resection of the pericardium. The radiation therapy target volume was the entire hemithorax, including the pleural folds and the thoracotomy and chest tube incision sites. Patients were treated with a total dose of 5400 cGy delivered in 30 fractions of 180 cGy. Radiation therapy was well tolerated, and toxicity data are described. RESULTS: Of the 35 patients analyzed, 29 patients were male, and 18 had right-sided tumors. Twenty-six had epithelioid histologies. UICC stage was I in 4, II in 11, III in 19, and IV in 1 patient. As shown by axial and sagittal isodose distributions, we were able to deliver adequate doses to the target volume while limiting dose to critical structures such as heart, spinal cord, liver, and stomach. The most common toxicities were RTOG Grades 1 and 2 nausea and vomiting, as well as lung, esophageal, and skin toxicities. CONCLUSION: Extrapleural pneumonectomy followed by high-dose hemithoracic radiation therapy is a feasible treatment regimen that is well tolerated for patients with malignant mesothelioma. We have demonstrated adequate dose distributions, using a combined photon and electron technique with blocking of critical normal structures.     

ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation expert panel on radiation oncology-head and neck cancer

Recurrent and second primary head-and-neck squamous cell carcinomas arising within or in close proximity to previously irradiated fields are a common clinical challenge. Whereas surgical salvage therapy is recommended for resectable disease, randomized data support the role of postoperative reirradiation in high-risk patients. Definitive reirradiation is an established approach for patients with recurrent disease who are medically or technically inoperable or decline radical surgery. The American College of Radiology Expert Panel on Head and Neck Cancer reviewed the relevant literature addressing re-treatment after prior definitive radiation and developed appropriateness criteria for representative clinical scenarios. Examples of unresectable recurrent disease and microscopic residual disease after salvage surgery were addressed. The panel evaluated the appropriateness of reirradiation, the integration of concurrent chemotherapy, radiation technique, treatment volume, dose, and fractionation. The panel emphasized the importance of patient selection and recommended evaluation and treatment at tertiary-care centers with a head-and-neck oncology team equipped with the resources and experience to manage the complexities and toxicities of re-treatment.     

Arterial baroreflex and peripheral chemoreflex function after radiotherapy for laryngeal or pharyngeal cancer

: Denervation of the carotid sinus causes baroreflex and chemoreflex failure, resulting in labile hypertension and loss of hypoxic responsiveness. We investigated whether radiation therapy for laryngeal or pharyngeal cancer affects baroreflex and chemoreflex function.

: Twelve patients were studied after radiation therapy for locally advanced laryngeal or pharyngeal cancer (11 male, 1 female, age: 56.0 ± 7.9 years), 3.3 years (median; range 1.0–4.7) after radiotherapy and 15 healthy controls (11 male, 4 female, 53.4 ± 9.2 years). We measured baroreflex sensitivity (phenylephrine), blood pressure level and variability (24-h Spacelabs and 5-h Portapres recordings), responses to cardiovascular reflex tests, and the ventilatory responses to normocapnic and hypercapnic hypoxia.

: Baroreflex sensitivity was lower in patients (9.7 ± 7.8 ms/mm Hg) than in controls (17.5 ± 10.3 ms/mm Hg, p = 0.011). Mean office blood pressure was significantly higher in patients (141.5 ± 27.8/89.2 ± 10.6 mm Hg, 63.3 ± 12.3 bpm) than in controls (117.3 ± 10.1/75.1 ± 6.8 mm Hg, 61.8 ± 10.8 bpm). Blood pressure variability was not different between groups, nor were the responses to reflex tests. The normo/hypercapnic ventilatory response to hypoxia was similar in patients (0.21 ± 0.10/1.37 ± 0.60 L/min/%) and controls (0.22 ± 0.16/1.19 ± 0.78 L/min/%).

: Radiation therapy for laryngeal or pharyngeal carcinoma does not affect chemoreflex function, but results in an attenuated baroreflex sensitivity. Clinically relevant blood pressure lability is absent however.     

Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314

Following documented evidence of the synergism of 5-fluorouracil (5-FU) and radiation therapy and an additive effect with mitomycin and irradiation, pilot studies have demonstrated the potential for definitive radiation therapy in the management of squamous cell and basaloid carcinomas of the anal canal, allowing sphincter preservation. Our study explored the long-term effectiveness of combined therapy at this disease site and examined the feasibility of a Radiation Therapy Oncology Group study involving concomitant radiation therapy and chemotherapy. Between 1983 and 1987, 79 assessable patients with any primary tumor stage of anal canal carcinoma were treated by external-beam irradiation combined with mitomycin given by bolus iv injection and 5-FU given by continuous infusion. Radiation was delivered to the perineum and pelvis to a total dose of 4,080 cGy in 4.5-5 weeks. The inguinal nodal areas received 4,080 cGy, calculated at a 3-cm depth in the center of the nodal area. A 96-hour infusion of 5-FU was started on days 2 and 28 of the irradiation at a dose of 1,000 mg/m2 over 24 hours, and a bolus injection of mitomycin was administered on day 2 at a dose of 10 mg/m2. The overall survival rates are 97% at 1 year and 73% at 3 years. Patients with lesions less than 3 cm in diameter and those treated strictly according to the protocol did significantly better than those with larger lesions and those whose treatment did not comply with the protocol. The interim outcome of the study demonstrates that this combined therapy is effective for patients with anal cancer and allows preservation of the sphincter and of sexual function.     

Choosing an intensity-modulated radiation therapy technique in the treatment of head-and-neck cancer

PURPOSE: With the emerging use of intensity-modulated radiation therapy (IMRT) in the treatment of head-and-neck cancer, selection of technique becomes a critical issue. The purpose of this article is to establish IMRT guidelines for head-and-neck cancer at a given institution. METHODS AND MATERIALS: Six common head-and-neck cancer cases were chosen to illustrate the points that must be considered when choosing between split-field (SF) IMRT, in which the low anterior neck (LAN) is treated with an anterior field, and the extended whole-field (EWF) IMRT in which the LAN is included with the IMRT fields. For each case, the gross tumor, clinical target, and planning target volumes and the surrounding critical normal tissues were delineated. Subsequently, the SF and EWF IMRT plans were compared using dosimetric parameters from dose-volume histograms. RESULTS: Target coverage and doses delivered to the critical normal structures were similar between the two different techniques. Cancer involving the nasopharynx and oropharynx are best treated with the SF IMRT technique to minimize the glottic larynx dose. The EWF IMRT technique is preferred in situations in which the glottic larynx is considered as a target, i.e., cancer of the larynx, hypopharynx, and unknown head-and-neck primary. When the gross disease extends inferiorly and close to the glottic larynx, EWF IMRT technique is also preferred. CONCLUSION: Depending on the clinical scenario, different IMRT techniques and guidelines are suggested to determine a preferred IMRT technique. We found that having this treatment guideline when treating these tumors ensures a smoother flow for the busy clinic.     

喉癌全喉切除术后局部复发的临床特点和治疗转归

目的　了解喉癌全喉切除术后局部复发的临床特点和治疗效果。方法　回顾性分析 1989年～ 1996年 193例喉癌进行全喉切除术患者的临床资料 ,对术后局部复发的 18例患者进行总结 ,明确局部复发的部位、时间以及再次治疗的效果。结果　全喉切除术后 18例 (9.3 % )患者出现局部复发。局部复发部位 :气管造瘘口复发 6例 (3 3 .3 % )、咽复发 11例 (61.1% )、气管造瘘口合并咽复发 1例 (5 .6% )。复发患者中有 2例同时合并颈段食管受累 (11.1% )。局部复发的时间为 6～ 2 0个月 ,平均 10 .2个月。复发患者的 3年和 5年累计生存率分别为 2 0 .0 %和 0。复发后距死亡的间隔时间为 2～ 5 1个月 ,平均 2 3 .7个月。造瘘口复发和咽复发患者的 3年生存率分别为 3 3 .3 % (2 /6)和 63 .6% (7/11)。术后复发患者再次行局部手术的 7例生存均超过 3年 ,经再手术治疗和非手术治疗的局部复发患者的生存率相互比较有显著性差异 (P <0 .0 5 )。结论　全喉切除术后局部复发主要包括造瘘口和咽部复发。局部复发后的预后很差。咽部复发者较造瘘口复发者预后好 ,应采取更积极的手术治疗