Differential diagnosis and treatment options in paranasal sinus cancers

Paranasal sinus malignancies are challenging to treat. Most patients present with advanced lesions, often with intracranial or intraorbital extension, and have a poor overall prognosis. Given the low incidence and diverse pathologies of paranasal sinus cancers, it is extremely difficult to perform prospective, randomized clinical trials to compare different treatment approaches. Improving the prognosis of these cancers continues to be a difficult task, even in light of advances in surgical techniques,radiation delivery techniques, and new chemotherapeutic agents. Cranio-facial resection techniques developed in the past few decades have cured many patients with skull base invasion, who would have been considered unresectable in the past. Furthermore, improvements in radiation therapy can allow more accurate administration to the desired region, with decreased damage to surrounding structures such as the orbit and brain.Aggressive and oncologically sound surgical resection combined with radiation therapy remains the treatment of choice for most patients.Finally, advances in the diagnosis and staging by use of molecular or DNA markers of tumor behavior may allow for more directed therapy.     

The use of acrylic resin oral prosthesis in radiation therapy of oral cavity and paranasal sinus cancer

In radiation therapy of cancers of the oral cavity and the paranasal sinuses, the extent to which the tissues of the oral cavity are included in the radiation treatment portals will determine the severity of the oral discomfort during treatment. This will affect the nutritional status of the patients, and may eventually affect the total dose of radiation which the patients can receive for treatment of their cancers. In cooperation with the Maxillofacial Prosthetic Department, an acrylic resin oral prosthesis was developed. This prosthesis is easy to use and can be made for each individual patient within 24 hours. It allows for maximum sparing of the normal tissues in the oral cavity and can be modified for shielding of backscattered electrons from heavy metals in the teeth. We have also found that acrylic resin extensions can be built onto the posterior edge of post-maxillectomy obturators; this extension can be used as a carrier for radioactive sources to deliver radiation to deep seated tumor nodules in the paranasal sinuses.     

Treatment of nasal cavity and paranasal sinus cancer with modern radiotherapy techniques in the postoperative setting--the MSKCC experience

PURPOSE: To perform a retrospective analysis of patients with paranasal sinus (PNS) cancer treated with postoperative radiotherapy (RT) at Memorial Sloan-Kettering Cancer Center. METHODS AND MATERIALS: Between January 1987 and July 2005, 85 patients with PNS and nasal cavity cancer underwent postoperative RT. Most patients had squamous cell carcinoma (49%; n = 42), T4 tumors (52%; n = 36), and the maxillary sinus (53%; n = 45) as the primary disease site. The median radiation dose was 63 Gy. Of the 85 patients, 76 underwent CT simulation and 53 were treated with either three-dimensional conformal RT (27%; n = 23) or intensity-modulated RT (35%; n = 30). Acute and late toxicities were scored according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria. RESULTS: With a median follow-up for surviving patients of 60 months, the 5-year estimates of local progression-free, regional progression-free, distant metastasis-free, disease-free, and overall survival rates were 62%, 87%, 82%, 55%, and 67%, respectively. On multivariate analysis, squamous cell histology and cribriform plate involvement predicted for an increased likelihood of local recurrence, and squamous cell histologic features predicted for worse overall survival. None of the patients who underwent CT simulation and were treated with modern techniques developed a Grade 3-4 late complication of the eye. CONCLUSION: Complete surgical resection followed by adjuvant RT is an effective and safe approach in the treatment of PNS cancer. Emerging tools, such as three-dimensional conformal treatment and, in particular, intensity-modulated RT for PNS tumors, may minimize the occurrence of late complications associated with conventional RT techniques. Local recurrence remains a significant problem.     

Intraoperative high-dose-rate brachytherapy for paranasal sinus tumors

PURPOSE: Advanced and recurrent tumors of the paranasal sinuses can be difficult to irradiate to high doses with standard external beam radiotherapy (EBRT), conventional brachytherapy, or intraoperative electron beams. We, therefore, explored the role of intraoperative high-dose-rate brachytherapy (IOHDR) as a boost to EBRT in primary tumors or as sole adjuvant treatment in recurrent disease. METHODS AND MATERIALS: Between 1992 and 1998, 34 patients with locally advanced tumors arising in the paranasal sinuses were treated with IOHDR after maximal surgical excision. Twenty-seven patients with new primaries underwent gross resection and 10-12.5 Gy IOHDR followed by 45-50 Gy EBRT. Seven previously irradiated (45-63 Gy) patients with recurrent disease were treated with 15-20 Gy of IOHDR alone after gross excision. Local control and overall survival were analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: After a mean follow-up of 6 years (range 34-120 months), the 1-, 3-, and 5-year actuarial survival rate was 80%, 62%, and 44%, respectively. The overall local control rate at 1 and 5 years was 75% and 65%, respectively, and distant failure was documented in 44% of patients. Subgroup analysis revealed that the presence of gross disease after surgical resection was the strongest prognosticator, with a 5-year survival and local control rate of 17% and 50%, respectively, compared with 60% and 68%, respectively, for microscopic disease. The local control rates of patients with new primaries were similar to those of patients treated for recurrent disease (63% vs. 71%), probably because gross residual disease occurred only in the group of patients with new primaries. The addition of EBRT to IOHDR increased the 5-year disease-free survival rate from 27% to 44% but had no effect on local control (64% vs. 65%). CONCLUSION: IOHDR can be safely used to deliver a high radiation dose to locally advanced and recurrent tumors in the paranasal sinuses. In an attempt to improve outcome, we are now adding limited-dose EBRT (20-30 Gy) after 17.5 Gy of IOHDR in previously irradiated patients and increasing the EBRT dose for both microscopic (50-54 Gy) and gross residual disease (60-65 Gy) after 15 Gy of IOHDR in previously unirradiated patients. Chemosensitization should also be considered in previously irradiated patients and in those with gross residual disease. Interstitial boosting techniques, which can deliver higher doses at depth, should also be considered in patients with gross residual disease.     

The risk of lymphedema after postoperative radiation therapy in endometrial cancer

Objective

Lower extremity lymphedema adversely affects quality of life by causing discomfort, impaired mobility and increased risk of infection. The goal of this study is to investigate factors that influence the likelihood of lymphedema in patients with endometrial cancer who undergo adjuvant radiation with or without chemotherapy.

Methods

A retrospective chart review identified all stage I–III endometrial cancer patients who had a hysterectomy with or without complete staging lymphadenectomy and adjuvant radiation therapy between January 2006 and February 2013. Patients with new-onset lymphedema after treatment were identified. Logistic regression was used to find factors that influenced lymphedema risk.

Results

Of 212 patients who met inclusion criteria, 15 patients (7.1%) developed new-onset lymphedema. Lymphedema was associated with lymph-node dissection (odds ratio [OR], 5.6; 95% CI, 1.01 to 105.5; p=0.048) and with the presence of pathologically positive lymph nodes (OR, 4.1; 95% CI, 1.4 to 12.3; p=0.01). Multivariate logistic regression confirmed the association with lymph-node positivity (OR, 3.2; 95% CI, 1.0007 to 10.7; p=0.0499) when controlled for lymph-node dissection. Median time to lymphedema onset was 8 months (range, 1 to 58 months) with resolution or improvement in eight patients (53.3%) after a median of 10 months.

Conclusion

Lymph-node positivity was associated with an increased risk of lymphedema in endometrial cancer patients who received adjuvant radiation. Future studies are needed to explore whether node-positive patients may benefit from early lymphedema-controlling interventions.     

Comparison of pre- and postoperative radiation in the combined treatment of carcinoma of maxillary sinus

A series of 50 patients with cancer of the maxillary sinus treated by either preoperative or postoperative radiation from February, 1958 to June, 1974 is presented. In the postoperative group the patients were either free from recurrence, of if there was recurrence, the tumor was less than 0.5 cm in diameter. In the preoperative group, 23 of 36 patients survived for more than five years (64 % ). In the postoperative group, 4 of 14 patients survived for more than five years (26%). There is an obvious superiority in the preoperative radiation group. The surgical complication rate in the preoperative group was 29% as compared to 14% in the postoperative group. Although the incidence of complications in the preoperative group is higher, we believe it is worth attempting in clinical practice because of the more favorable survival rates.     

鼻腔副鼻窦恶性肿瘤术后放疗临床分析

目的 探讨影响鼻腔副鼻窦恶性肿瘤术后放疗效果与预后的因素.方法 95例鼻腔副鼻窦恶性肿瘤接受术后放疗,生存率计算采用Kaplan-Meier法,生存率差异检验采用Logrank法,多因素分析采用Cox模型.结果 1,3,5,10年总生存率分别为84.2%、50.5%、44.2%和20.0%.单因素分析显示,性别、年龄、手术方法和肿瘤剂量与生存率无相关性;而临床分期、病理类型与生存率相关.多因素分析显示,临床分期、病理类型是影响预后的独立因素.视力障碍、听力障碍、口干是治疗的主要毒副作用.结论 临床分期、病理类型是影响鼻腔副鼻窦恶性肿瘤术后放疗效果和预后的重要因素,术后放疗能够提高鼻腔副鼻窦恶性肿瘤的疗效.     

Chondrosarcoma of the larynx after radiation treatment for vocal cord cancer

The case of a 57-year-old man with chondrosarcoma of the laryngeal cartilage is presented, occurring 16 years after radiation treatment for squamous cell carcinoma of the right true vocal cord. Chondrosarcoma of the larynx is an uncommon tumor. The location, grade, and time elapsed from initial treatment make it probably that this patient's chondrosarcoma is associated with his prior radiation treatment. However, it is a rare occurrence, this being the second case reported in the literature.     

Conformal three-dimensional photon radiotherapy for paranasal sinus tumors.

BACKGROUND: Tumors in the nasal cavity and paranasal sinus are difficult to treat with radiotherapy. Usually, in addition to a two- or three-field photon technique, an interorbital electron field is required. This may result, however, in severe over- or underdosage, the latter being especially detrimental when occurring in the main tumor bulk. METHODS AND RESULTS: We present a conformal three-dimensional treatment technique that provides sufficient interorbital dose with photons only while sparing the eyes, optic nerves and chiasm, and may be considered for selected tumors in this region.     

Ocular and orbital complications following radiation therapy of paranasal sinus malignancies and review of literature

During the period from March 1963 through March 1978, 30 patients with malignant neoplasms of the paranasal sinuses were treated with supervoltage technique at the University of Rochester Medical Center. Twenty-one patients had at least the medial portion of the orbit within the effective treatment volume and the rest of the patients had whole eye irradiation. In paranasal sinus malignancies, orbital involvement with ocular symptoms and signs is quite common; in many patients it can be the presenting problem. Enucleation is necessary in patients with gross orbital tumor. Eye preservation is worthwhile in patients with minimal orbital tumor. Anterior complications are a minimal risk if the technique is good. Posterior complications occur in almost all patients, but are rarely clinically significant until doses of 6000 rad or above are reached. In patients without gross orbital involvement, preservation of the eye can be considered optional treatment. It includes shielding of the anterior structures, but it is usually not possible to protect medial and posterior portions of the eye and orbit. In advanced cases, it is worthwhile to preserve the eye as cure rate is low and posterior eye complications are often late. Because the aim of treatment is cure, dose should not be compromised to prevent complications. Radiation injury to the optic nerve and retina is the major factor in visual loss, but it can be prevented by limiting the retinal and optic nerve dose to less than 6000 rad.     

Brief chemotherapy, involved field radiation therapy, and central nervous system prophylaxis for paranasal sinus lymphoma.

Lymphoma of the paranasal sinus is a rare tumor characterized by bulky local disease, early systemic dissemination, and a propensity for central nervous system (CNS) spread. Treatment with radiation alone generally has been disappointing. Based on previous encouraging reports of initial brief chemotherapy followed by involved field radiation therapy (IFRT) for localized large cell lymphoma, four consecutive patients with paranasal sinus lymphoma were treated with 6 weeks of chemotherapy followed by IFRT and CNS prophylaxis. All patients had bulky localized disease and diffuse large cell lymphoma. Complete response was seen in all patients, and none have had a relapse (minimum follow-up, 25 months; range, 25 to 32 months). Chemotherapy and radiation therapy were well tolerated. One patient developed an osteogenic sarcoma in the radiation field 32 months after completion of therapy. Administration of early frequent chemotherapy followed by IFRT and CNS prophylaxis appears to be an effective treatment strategy for patients with localized large cell lymphoma of the paranasal sinuses.     

Comparison of treatment plans using intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for paranasal sinus carcinoma

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conformal radiotherapy (3D-CRT) planning for paranasal sinus carcinoma. MATERIALS AND METHODS: Treatment plans using traditional 3-field technique, 3D-CRT planning, and inverse planning IMRT were developed for a case of paranasal sinus cancer requiring adjuvant radiotherapy. Plans were compared with respect to dose conformality, dose-volume histograms, doses to critical normal tissues, and ease of treatment delivery. RESULTS: The inverse-planned IMRT technique was more conformal around the tumor target volume than conventional techniques. The dose-volume histograms demonstrated significantly better critical normal-tissue sparing with the IMRT plans, while able to deliver a minimum dose of 60 Gy to the clinical tumor volume and 70 Gy to the gross tumor volume. Acute toxicities in our analysis were minimal. CONCLUSIONS: IMRT planning provided improved tumor target coverage when compared to 3D-CRT treatment planning. There was significant sparing of optic structures and other normal tissues, including the brainstem. Inverse planning IMRT provided the best treatment for all paranasal sinus carcinomas, but required stringent immobilization criteria. Further studies are needed to establish the true clinical advantage of this modality.     

PSA after radiation for prostate cancer

The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in the end points used for outcome reporting after therapy. With regard to a definition of failure after radiation, a consensus was reached in 1996 that took into account the particular issues of an intact prostate after therapy. Over the next several years, the consensus definition issued by the American Society for Therapeutic Radiology and Oncology (ASTRO) was used and studied. Concerns and criticisms were raised. The sensitivity and specificity of this definition vs other proposals has been investigated, and differences in outcome analyzed and compared. Although the ASTRO definition came from analysis of datasets on external-beam radiation and most of the work on this topic has been with this modality, failure definitions for brachytherapy must be explored as well. The concept of a universal definition of failure that might be applied to multiple modalities, including surgery, should also be investigated, at least for comparative study and research purposes.     

Patterns of failure after resection of non-small-cell lung cancer: implications for postoperative radiation therapy volumes

PURPOSE: To analyze local-regional patterns of failure after surgical resection of non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: This retrospective analysis included 61 patients who underwent resection of NSCLC at Duke University Medical Center. Inclusion into the study required the following: margin-negative resection, no neoadjuvant/adjuvant radiation therapy (RT), first recurrence involving a local-regional site, and imaging studies available for review. Sites of intrathoracic disease recurrence were documented. Diagrams were constructed that illustrated sites of failure on the basis of lobe of primary tumor. Failure rates were compared by application of a two-tailed Fisher's exact test. RESULTS: All patients had CT imaging for review, and 54% also had PET imaging. The median number of local-regional recurrent sites was two (range, 1-6). For all patients, the most common site of failure was the bronchial stump/staple line (44%), which was present more often in those who had a wedge resection than in those who had a more radical procedure (79% vs. 34%, p=0.005). Patients with initial nodal involvement (pN1-2) were not more likely to have involvement of the mediastinum than were patients with pN0 disease (64% vs. 72%, p=0.72), but were more likely to have involvement of the supraclavicular fossa (27% vs. 4%, p=0.04). Mediastinal involvement, without overt evidence of hilar involvement, occurred in 59% of patients. Left-sided tumors tended to involve the contralateral mediastinum more frequently than did right-sided tumors. Patterns of failure after resection are diagrammed and follow a fairly predictable pattern on the basis of involved lobe. CONCLUSIONS: These data may help clinicians construct postoperative RT volumes that are smaller than ones traditionally utilized, which may improve the therapeutic ratio.     

Locally advanced paranasal sinus and nasopharynx tumors treated with hyperfractionated radiation and concomitant infusion cisplatin.

Fourteen patients with paranasal sinus complex and nasopharynx tumors were treated at State University of New York Health Science Center at Brooklyn (Brooklyn, NY) with a regimen of split-course hyperfractionated radiation (120 cGy/fraction) and concomitant cisplatin infusion (5 to 7 mg/m2/24 hours). All of the patients had T4 tumors or massively recurrent disease with base of skull or facial bone involvement. Twelve patients were treated with curative intent receiving total doses of 6000 to 6960 cGy (modal 6750 cGy), whereas two patients were treated with less than 5000 cGy as palliation. Eleven of the 12 patients (92%) achieved a complete response, and 7 of 12 (58%) are alive at 35 to 72 months (mean, 47 months). Five patients are alive with no evidence of disease, and two with a local recurrence. Three patients died of distant disease, and two died from a local recurrence. When the response to treatment was analyzed based on tumor volume and radiation dose, only two of nine lesions measuring between 4 to 10 cm failed locally. The two palliative patients had almost complete local clearance of the disease but died at 2 and 8 months, respectively. In nine patients, the eye or optic nerve was included in the treatment field and received between 2000 to 6960 cGy. Only one of these nine patients had ophthalmic complication and this was confined to the cornea.