Transanal total mesorectal excision and delayed coloanal anastomosis without stoma for low rectal cancer.

The management of low rectal cancer is a perennial challenge for colorectal surgeons. The benefits of transanal total mesorectal excision (TaTME) in low rectal cancer are to secure the distal margin and avoid surgical space constraints within the deep pelvis. However, anastomotic leak remains an important concern. We report our technique and results combining TaTME with delayed coloanal anastomosis (DCAA) without bowel diversion. First, the splenic flexure, left colon and rectum are laparoscopically mobilized to mid-rectum. TaTME is performed to complete the distal rectal mobilization, and the specimen is delivered transanally and transected. The abdominoperineal colonic pull-through is secured to the anal canal and hypertonic dressing is applied regularly in the ward. The handsewn DCAA is performed one week later. An accompanying video demonstrates this technique. Five consecutive patients with low rectal cancer underwent TaTME with DCAA. All had upfront surgical resection except one who underwent total neoadjuvant therapy. Mean operative duration, blood loss, and length of hospital stay was 290 (250-375) min, 142 (10-200) ml and 11.6 (10-14) days respectively. One patient (20%) suffered a postoperative complication of persistent urinary retention, requiring an indwelling urinary catheter on discharge. There were no cases of open conversion and no instances of anastomotic leakage. Two patients (40%) had minor low anterior resection syndrome (LARS) and one (20%) had major LARS. TaTME and DCAA without stoma are complimentary techniques that augment the minimally invasive effects of laparoscopic sphincter-sparing low rectal cancer surgery, with good perioperative outcomes.

A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial.

Background: Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse. Patients and methods: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort. Results: Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings. Conclusions: These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.

Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (Chinese Society of Clinical Oncology), Korea (Korean Association for Clinical Oncology), Malaysia (Malaysian Oncological Society), Singapore (Singapore Society of Oncology) and Taiwan (Taiwan Oncology Society). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

[The role of photodynamic therapy for the treatment of stage I and II carcinoma of the lip]. / De rol van fotodynamische therapie bij de behandeling van het stadium I en II lipcarcinoom.

In this research project the outcomes of photodynamic therapy for the treatment of stage I and II carcinoma of the lip are presented. Retrospectively, 15 patients diagnosed with a primary stage I or II lip carcinoma and treated with meta-tetra hydroxyphenyl chlorin mediated photodynamic therapy were evaluated. The primary outcome measure was disease free survival; the secondary outcome measure was the functional and aesthetic outcome after treatment. A total of 16 primary lip carcinomas were evaluated (75% stage I; 25% stage II). In 94% of the primary lip carcinomas, photodynamic therapy led to a complete remission after a variable follow-up of 14 months to 11 years. The functional and aesthetic long-term outcomes were considered excellent. Photodynamic therapy for the treatment of stage I and II lip carcinoma has a disease free survival rate comparable to surgery or radiotherapy and has outstanding functional and aesthetic outcomes.

The role of Indonesian patients' health behaviors in delaying the diagnosis of nasopharyngeal carcinoma.

BACKGROUND: With an estimated 13,000 newly diagnosed patients per year, nasopharyngeal carcinoma (NPC) is one of the most common types of cancer in males in Indonesia. Moreover, most patients are diagnosed at an advanced stage of the disease. This study aimed to explore the health behaviors of patients diagnosed with NPC and the possible causes of patient delay in NPC diagnosis. METHODS: A qualitative research method was used to gain better insight into patient behaviors. Twelve patients were interviewed using semi-structured interview guidelines. All interviews were recorded, transcribed verbatim and analyzed according to a standard content analysis framework. RESULTS: Most patients had limited knowledge regarding NPC and its causes. Fifty percent of the patients had a delay of six months from the onset of symptoms to diagnosis. The main reason for this delay was the lack of awareness among the patients, which was influenced by their environment, economic status, family, culture, and religion. The perceived barriers to seeking medical help included direct non-medical costs not covered by health insurance, complex and time-consuming insurance and referral systems, and negative experiences in the past. Health insurance did motivate people to seek medical help. CONCLUSION: This study provides additional insight into patients' motivations to delay seeking medical help and can facilitate the design of NPC education programs. To improve awareness of the abovementioned causes for delay, community-based education programs are highly warranted and should focus on the recognition of NPC symptoms and possible solutions to overcome the main barriers at an earlier disease stage.

Palliative surgical intervention in metastatic colorectal carcinoma: a prospective analysis of quality of life.

AIM: Quality of life (QOL) was assessed after palliative surgery for incurable metastatic colorectal cancer (CRC). METHOD: Newly diagnosed patients with incurable metastatic CRC who were offered elective palliative surgical intervention were included. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaire was used for the assessment of QOL at baseline and at 3 and 6 months after surgery. Generalized estimating equations were used to estimate the mean change in the QOL score from baseline. RESULTS: Twenty-four patients formed the study group. Sixteen underwent resection of the primary tumour and eight had a proximal diversion or bypass. The Global Health (GH) score and Social Functioning (SF) score improved at 3 and 6 months after intervention respectively (GH +11, P = 0.021; SF +15, P = 0.005). Mean anxiety scores were markedly improved from the baseline of 51 to 71 (P = 0.004, 3 months) and 76 (P = 0.002, 6 months). Weight concerns also improved significantly when compared with baseline (3 months, +20, P < 0.001; 6 months, +14, P = 0.012). Symptoms of diarrhoea (3 months, --17, P = 0.007; 6 months,--16, P = 0.008) and nausea (--8, P = 0.032) improved. CONCLUSION: In patients with incurable metastatic CRC, surgery improved QOL.

KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study.

BACKGROUND: Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions. METHODS: The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed. RESULTS: Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC. CONCLUSIONS: This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.

Current treatment options for local residual nasopharyngeal carcinoma.

OPINION STATEMENT: Local residual disease occurs in 7-13 % after primary treatment for nasopharyngeal carcinoma (NPC). To prevent tumor progression and/or distant metastasis, treatment is indicated. Biopsy is the "gold standard" for diagnosing residual disease. Because late histological regression frequently is seen after primary treatment for NPC, biopsy should be performed when imaging or endoscopy is suspicious at 10 weeks. Different modalities can be used in the treatment of local residual disease. Interestingly, the treatment of residual disease has better outcomes than treatment of recurrent disease. For early-stage disease (rT1-2), treatment results and survival rates are very good and comparable to patients who had a complete response after the first treatment. Surgery (endoscopic or open), brachytherapy (interstitial or intracavitary), external or stereotactic beam radiotherapy, or photodynamic therapy all have very good and comparable response rates. Choice should depend on the extension of disease, feasibility of the treatment, and doctor's and patient's preferences and experience, as well as the risks of the adverse events. For the more extended tumors, choice of treatment is more difficult, because complete response rates are poorer and severe side effects are not uncommon. The results of external beam reirradiation and stereotactic radiotherapy are better than brachytherapy for T3-4 tumors. Photodynamic therapy resulted in good palliative responses in a few patients with extensive disease. Also, chemotherapeutics or the Epstein-Barr virus targeted therapies can be used when curative intent treatment is not feasible anymore. However, their advantage in isolated local failure has not been well described yet. Because residual disease often is a problem in countries with a high incidence of NPC and limited radiotherapeutic and surgical facilities, it should be understood that most of the above mentioned therapeutic modalities (radiotherapy and surgery) will not be readily available. More research with controlled, randomized trials are needed to find realistic treatment options for residual disease.

Recommendations for the use of next-generation sequencing in patients with metastatic cancer in the Asia-Pacific region: a report from the APODDC working group.

INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.

The indwelling voice prosthesis for speech rehabilitation after total laryngectomy: a safe approach.

Primary prosthetic voice restoration by performing tracheoesophageal puncture (TEP) and immediate insertion of a voice prosthesis at the time of total laryngectomy (TLE) is presently the method of choice. This enables the easiest and most comfortable voice rehabilitation with the patient still under general anesthesia when the first prosthesis is inserted. Reconstruction of the pharynx with e.g. free revascularized or pedicled flaps does not preclude surgical prosthetic voice restoration. The TEP can even be done as a primary procedure after total laryngectomy and total pharyngectomy when the full circumference of the neopharynx has to be reconstructed, provided the esophagus is still present at the level of the trachea. Since indwelling devices may have a more robust construction, their device-life generally is longer than that of their non-indwelling counterparts. Indwelling devices have the unique advantage in that patient's dexterity plays a lesser role in the daily maintenance of the device. With a few refinements in the surgery of TLE several postlaryngectomy problems can be avoided or diminished such as hypertonicity of the pharyngoesophageal (PE) segment and a poor contour of the stoma. The combination of Heat and Moisture Exchanger (HME) and indwelling voice prosthesis contributes to a significant improvement of both pulmonary function and voice quality. The solution of the majority of prosthesis and TE-fistula related problems by the well trained physician, make prosthetic voice restoration a safe procedure.

Intra-cavity Photodynamic Therapy for malignant tumors of the paranasal sinuses: An in vivo light dosimetry study.

BACKGROUND: Photodynamic therapy (PDT) is a promising treatment option for recurrent sinonasal malignancies. However, light administration in this area is challenging given the complex geometry, varying tissue optical properties and difficult accessibility. The goal of this study was to estimate the temporal and spatial variation in fluence and fluence rate during sinonasal mTHPC-mediated PDT. It was investigated whether the predetermined aim to illuminate with a fluence of 20 J⋅cm-2 and fluence rate of 100 mW⋅cm-2 was achieved. METHODS: In eleven patients the fluence and fluence rates were measured using in vivo light dosimetry at the target location during real-time sinonasal PDT. There was a variance in sinonasal target location and type of light diffuser used. In four patients two isotropic detectors were used within the same cavity. RESULTS: All measurements showed major fluence rate fluctuations within each single isotropic detector probe over time, as well as between probes within the same cavity. The largest fluence rate range measured was 328 mW⋅cm-2. Only one probe showed a mean fluence rate of ∼100 mW⋅cm-2. Taken all probes together, a fluence rate above 80 mW⋅cm-2 was measured in 31 % of the total light exposure; in 22 % it was less than 20 mW⋅cm-2. Thirty-three percent showed a fluence of at least 20 J⋅cm-2. CONCLUSIONS: The current dosimetry approach for sinonasal intra-cavity PDT shows major temporal and spatial variations in fluence rate and a large variance in light exposure time. The results emphasize the need for improvement of in vivo light dosimetry and dosimetry planning.

The surgical dilemma of 'functional inoperability' in oral and oropharyngeal cancer: current consensus on operability with regard to functional results.

OBJECTIVES: If surgical resection of a tumour results in an unacceptable loss of function, this is defined as 'functional inoperability'. The current survey aims to define the borders of functional inoperability in oral and oropharyngeal carcinoma and evaluate its current use by obtaining opinions from the experts in the field. DESIGN: A web base survey. PARTICIPANTS: Dutch head-neck surgeons and radiotherapists. MAIN OUTCOME MEASURES: Assessment of functional results after tumour resection in twenty-two statements and five cases. RESULTS: Response on the survey is 93% and the reactions are variable. Reactions vary slightly by the size of the clinic or discipline (radiation oncology versus head and neck surgery). There is agreement about the unacceptable function loss after total glossectomy. There is no absolute consensus about the functional outcome after certain surgical procedures, namely: bilateral maxillectomy, resection of a tonsil and resection of base of tongue carcinoma including removal of the vallecula and epiglottis, and total soft palate resection. Disagreement of operability is also observed for T3 and T4 base of tongue carcinomas based on case descriptions and Magnetic Resonance Images. Assessment of whether one hypoglossal nerve can be preserved is agreed to be a key factor for functional operability. CONCLUSIONS: The term functional inoperability appears to be clinically used by Dutch experts in the decision making process in advanced head and neck carcinomas. According to the experts who took part in the survey, primary total glossectomy or sacrificing both hypoglossal nerves is an operation that causes too much and therefore unacceptable function loss. In several case scenarios a consensus over operability could not be reached by the experts. The decision varies per physician, institute and patient. Functional inoperability is variable and difficult to determine, but it is clinically used and therefore important to bring under attention.

In vivo fluence rate measurements during Foscan-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator.

The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study. We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area. A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light. Fourteen patients were included in the study, resulting in 26 fluence rate measurements in the risk volume (two failures). We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy-induced increased blood content, decreased oxygenation, or reduced scattering. Our findings demonstrate that the applicator was easily inserted into the nasopharynx. The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity. Shielding of the risk area was adequate. Large interpatient variations in fluence rate stress the need for in vivo dosimetry. This enables corrections to be made for differences in optical properties and geometry resulting in comparable amounts of light available for Foscan absorption.

The Impact of the Overall Radiotherapy Time on Clinical Outcome of Patients with Nasopharyngeal Carcinoma; A Retrospective Study.

PURPOSE: In Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to radiotherapy treatment. Previous study showed a prolonged overall treatment time (OTT), due to interruptions during treatment. This study explores the association between clinical outcome and OTT. Secondary, the relation between clinical outcome and disease stage, waiting time to radiation (WT) and chemotherapy schedule was explored. METHODS: In this retrospective cohort, 142 patients who started curative intent radiotherapy for NPC between March 2009 and May 2014, with or without chemotherapy, were included. The median follow up time was 1.9 years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule. Time factors were log-transformed. Clinical outcome was defined as therapy response, loco-regional control (LRC), disease free survival (DFS) and overall survival (OS). RESULTS: The median WT was 117 days (range 12-581) and OTT was 58 days (43-142). OTT and disease stage were not associated to any of the clinical outcome parameters. The log-WT was associated to poor therapy outcome (HR 1.68; 95% ci: 1.09-2.61), LRC (HR 1.66; 95% ci: 1.15-2.39), and DFS (HR 1.4; 95% ci: 1.09-1.81). In the multivariable analysis, significant hazard risk for poor therapy response, LRC, DFS and OS were seen for patients who didn't received concurrent chemotherapy. CONCLUSION: Not receiving concurrent chemotherapy showed the strongest risk for poor outcome. Since the choice of chemotherapy is related to a variety of factors, like the WT and patient's physical condition when radiation can start, careful interpretation is needed. Reason for not finding a relation between OTT and clinical outcome might be the low number of patients who finished radiotherapy within 7 weeks, or by a stronger detrimental effect of other factors.

The use of photodynamic therapy as adjuvant therapy to surgery in recurrent malignant tumors of the paranasal sinuses.

BACKGROUND: Malignant tumors of paranasal sinuses and anterior skull base recur frequently after surgery and adjuvant radiotherapy. The vicinity of essential structures limits additional treatment options, such as salvage surgery and re-radiation. We report the feasibility of photodynamic therapy (PDT) as an adjuvant treatment to surgery. METHODS: Fifteen patients with recurrent tumors of the paranasal sinuses were treated with mtetrahydroxyphenylchlorin (mTHPC) mediated PDT as an adjuvant treatment to salvage surgery. All patients had previously curative radiotherapy. The treated tumors were squamous cell cancer (8), adenocarcinoma (3), undifferentiated carcinoma (2), adenoid cystic carcinoma (1) and radiotherapyinduced sarcoma (1). In five cases there was extension to the skull base. Two approaches of surgery where used, namely in eight cases an open approach, in the other seven endoscopic approach. Complete macroscopic resection with microscopic tumor positive margins was possible in three patients. The remaining twelve patients received debulking surgery followed by PDT. RESULTS: None of the patients had cerebrospinal fluid leak, meningitis, major bleeding or vision loss. Four patients developed temporary diplopia due to edema of the medial rectus muscle, one patient suffered from extensive necrosis leading to oro-nasal fistula. Complete response was observed in five patients. CONCLUSION: Photodynamic therapy can be used with relative safety as adjuvant therapy to surgery in recurrent tumors of the paranasal sinuses and the anterior skull base where complete resection is not achievable.

Photodynamic therapy as salvage therapy for patients with nasopharyngeal carcinoma experiencing local failures following definitive radiotherapy.

BACKGROUND: Treating local failures of nasopharyngeal carcinoma (NPC) is a challenge. This study evaluates photodynamic therapy (PDT) in the treatment of residual and recurrent NPC. METHOD: In this phase II study, patients with local recurrent or residual NPC after curative intent (chemo-) radiation could be included. Exclusion criterion was a tumour depth more than 10mm. Foscan® 0.15mg/kg was administered intravenously. After 96h, the illumination was performed under local anaesthesia with a nasopharyngeal light applicator. Tumour response was measured 10 weeks after illumination by endoscopy, biopsy and CT-scan. Kaplan-Meier method was used for survival analysis. RESULTS: Twenty-one patients were included. Fourteen patients were treated for residual disease (67%), and two for recurrent (10%). For five patients this distinction could not be made, due to uncertainty about complete response after initial treatment. The median follow-up time was 32 months. Twenty patients (95%) had a complete response 10 weeks post-treatment. Two patients had recurrent local disease at 5 and 7 months post-PDT. They received another course of PDT, one with success. The 2-year local control rate was 75%, progression free survival was 49% and overall survival was 65%. Nine patients (43%) had no evidence of disease and were in a good clinical condition (ECOG Performance Scale 0) at the end of the study period. No serious adverse events were observed. CONCLUSION: This study showed that PDT is effective in treating local failures of NPC with a depth of less than 10mm. The treatment was easy to perform under local anaesthesia. Especially in regions were other modalities like radiation and surgery are limited PDT can be a good alternative treatment.

Does the combination of radiotherapy and debulking surgery favor survival in paranasal sinus carcinoma?

PURPOSE: To determine the contribution of debulking surgery on local control and survival in paranasal sinus tumors. As most patients present with locally advanced disease, the possibility of radical surgery is limited. Consequently, radiotherapy is often needed as monotherapy or as an adjunct to surgery. METHODS AND MATERIALS: Between 1977 and 1996, 73 patients (50 male: 23 female) with a paranasal sinus carcinoma were treated. The histology distribution was as follows: squamous cell carcinoma, 55%; adenocarcinoma, 19%; adenoid cystic carcinoma, 11%; and undifferentiated carcinoma, 15%. The clinical T classification was (UICC/TNM 1997): T2 14%, T3 27%, and T4 59%. Pathological neck nodes were found in 11% of patients. Treatment consisted of surgery only in 3, chemotherapy only in 1, radiotherapy only in 18, both surgery and radiotherapy in 50 patients. One patient did not receive any treatment at all. Three patients had concurrent chemotherapy. Median follow-up was 66 months (range, 1-213 months). RESULTS: Five-year local control (LC) was 65% with combination of radiotherapy and debulking surgery in comparison with 47% with radiotherapy alone, but this difference was not statistically significant (p = 0.58). However, combination treatment gave significantly better 5-year overall survival (OS) (60% vs. 9%; p = 0.001) and 5-year disease-free survival (DFS) (53% vs. 6%; p < 0. 0001). Cox-regression analysis showed that pathologic N status (p = 0.04), palliative intention of treatment (p = 0.018), clinical orbital invasion (p = 0.003), and orbital wall invasion (p = 0.003) were parameters significantly associated with poor local control. Total radiation dose of greater than 65 Gy (p = 0.05) and treatment consisting of radiotherapy alone (p = 0.002) were associated with worse overall survival; for disease-free survival clinical orbital invasion (p = 0.0005), age of greater than 65 years (p = 0.013) and pathologic T4 classification (p = 0.002) were significant factors for an unfavorable outcome. In 19 of 73 patients, 26 serious (mainly ophthalmological) complications were reported; in the majority of these, the visual tract was (partly) included in the treatment fields because of tumor extension. To analyze on which basis patients were selected for the combination therapy, a logistic regression was performed, concluding that clinical T4 classification (p = 0.05), radiological evidence of skull base invasion (p = 0.005), age of greater than 65 years (p = 0.026), radiological evidence of nasopharynx invasion (p = 0.02), clinical suspicion of palate invasion (p = 0.02), and radiological evidence of skin invasion (p = 0.009) were associated with choosing radiotherapy alone. CONCLUSION: Debulking surgery of paranasal sinus malignancies followed by high-dose radiotherapy to the involved sites was associated with better survival and (although not statistically significant) local control. Patient selection, based on clinical and radiological impression of tumor extension, was the main factor explaining these favorable results. We favor this combination regimen because the surgery gives quick relief of complaints and, at the same time, offers an excellent histologically proven staging method, enabling radiotherapy to be adjusted to the involved sites, thereby decreasing the risk of complications. This can all be achieved with a very low orbital exenteration rate.

Thallium-201 SPECT in the diagnosis of head and neck cancer.

UNLABELLED: The accuracy of SPECT with 201Tl-chloride for the diagnosis of primary tumors, lymph node metastases and recurrences in head and neck cancer was evaluated for clinical applicability. METHODS: SPECT images, obtained 60 min after administration of 150 MBq 201Tl-chloride, were compared with clinical, CT and/or MRI and histology results. In addition, whole-body images were obtained to detect distant metastases. RESULTS: In 79 patients studied for primary tumors (principally larynix, hypopharynx, oropharynx, nasopharynx and oral cavity), 201Tl SPECT correctly identified 69 of 73 (95% versus 88% for CT/MRI) histologically confirmed malignancies including 63 squamous-cell carcinomas. The method localized four occult naso- and oropharynx carcinomas not seen on CT/MRI and was correctly negative in two patients without tumor and in three of four patients with no confirmed primary tumor in the head and neck. With respect to regional spread, only patients who had cervical lymph node dissection were evaluated, and the findings were recorded per side of the neck. Thallium-201 SPECT correctly identified metastases in 31 of 36 neck dissections with proven lymph node involvement (86%), was correctly negative in nine and false-positive in one. Although the sensitivity of CT/MRI was clearly higher (97%), considerably more false-positive cases affected its accuracy (81% versus 87% for SPECT). In 30 patients investigated for recurrences, 201Tl SPECT correctly identified 27 of 29 microscopically confirmed tumor sites (93%) and was correctly negative in seven. Sensitivity of CT/MRI was lower (76%), and a greater number of false-positives (seven versus three for SPECT) further decreased its accuracy (64% versus 87% for SPECT). Distant metastases were detected in five patients. CONCLUSION: Thallium-201 SPECT appears to be an accurate method for the diagnosis of head and neck cancer. The method is particularly useful for detection of occult head and neck tumors and for assessing recurrences. It also may be of complementary value in the staging of primary tumors, in the differentiation of metastatic from reactive lymph nodes in the neck and, on the basis of whole-body scanning, for screening of distant metastases.