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BACKGROUND: Surgery is the primary treatment for patients with recurrent head and neck cutaneous squamous cell carcinoma (cSCC) who have previously been treated by definitive surgery and radiotherapy. There are limited published data to direct management and the role of immunotherapy is currently under evaluation. METHODS: This was a retrospective study of patients with at least stage III recurrent head and neck cSCC previously managed by definitive surgery and radiotherapy. RESULTS: A total of 30 patients met the inclusion criteria. Eighty-seven percent were male and the median age at the time of surgery was 79 years. After salvage surgery, 7% developed local recurrence and 43% regional or distant failure. The 2-year overall survival and disease-free survival were 45% (95% confidence interval 24-64) and 11% (95% confidence interval 1-34), respectively. Advanced age was associated with a higher risk of overall mortality (P

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in the immunocompromised host. Atypical presentations which include pseudotumors or "cancer mimics" have been described. The etiology of these lesions remains unclear. The authors describe two previously unpublished cases that have arisen in the context of newer immunomodulating therapy and review the existing non-HIV-associated CMV pseudotumors described in the literature.

INTRODUCTION TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin. METHODS Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET. RESULTS Fifty-eight subjects (45 males and 13 females, median age 68 years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival. CONCLUSION Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.

Background The aim of the present study was to identify the presence and frequency of human papillomavirus (HPV) nucleic acid in p16 positive oral squamous cell carcinomas (OSCC), to assess if the virus were transcriptionally active, and to assess the utility of p16 overexpression as a surrogate marker for HPV in OSCC. Methods Forty-six OSCC patients treated between 2007 and 2011 with available formalin-fixed paraffin embedded (FFPE) specimens were included. Twenty-three patients were positive for p16 by immunohistochemistry (IHC) and these were matched with 23 patients with p16 negative tumours. Laser capture micro-dissection of the FFPE OSCC tissues was undertaken to isolate invasive tumour tissue. DNA was extracted and tested for high-risk HPV types using a PCR-ELISA method based on the L1 SPF10 consensus primers, and a real-time PCR method targeting HPV-16 and HPV-18 E6 region. Genotyping of HPV positive cases was performed using a reverse line blot hybridization assay (Inno-LiPA). RNAScope® (a chromogenic RNA in situ hybridization assay), was utilized to detect E6/E7 mRNA of known high-risk HPV types for detection of transcriptionally active virus. Results HPV DNA was found in 3 OSCC cases, all of which were p16 IHC positive. Two cases were genotyped as HPV-16 and one as HPV-33. Only one of the HPV-16 cases was confirmed to harbour transcriptionally active virus via HPV RNA ISH. Conclusion We have shown that the presence of transcriptionally active HPV rarely occurs in OSCC and that p16 is not an appropriate surrogate marker for HPV in OSCC cases. We propose that non-viral mechanisms are responsible for the majority of IHC p16 overexpression in OSCC. This article is protected by copyright. All rights reserved.

This review evaluated the association between time-to-chemotherapy (TTC) and survival in six priority cancers. A systematic review of the literature was undertaken for papers indexed in the MEDLINE and Cochrane Library databases from the earliest index until April 2014. The methodology used has been published in a separate paper (Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services). The optimal timing of chemotherapy in breast cancer is unclear as available studies are of low quality, report inconsistent results and are limited to the adjuvant setting. However, increased TTC may have a negative prognostic impact, and delays beyond 4 weeks should be avoided. Studies suggest that the optimal timing for initiation of adjuvant chemotherapy for surgically resected colorectal cancer is 4-8 weeks post-surgery. Timing of chemotherapy for metastatic colorectal cancer does not influence survival. There is a paucity of studies to guide the timing of chemotherapy for the treatment of lymphoma and myeloma; no definitive conclusions can be drawn, and clinician discretion should be applied. The optimal timing of chemotherapy in lung cancer is unclear; however, rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible. The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level, report inconsistent results and are limited to the post-surgery setting; however, increased TTC may have a negative prognostic impact; therefore, delays beyond 4 weeks should be avoided.

These guidelines, informed by the best available evidence and consensus expert opinion, provide a framework to guide the timely initiation of chemotherapy for treating cancer. They sit at the intersection of patient experience, state-of-the-art disease management and rational efficient service provision for these patients at a system level. Internationally, cancer waiting times are routinely measured and publicly reported. In Australia, there are existing policies and guidelines relating to the timeliness of cancer care for surgery and radiation therapy; however, until now, equivalent guidance for chemotherapy was lacking. Timeliness of care should be informed, where available, by evidence for improved patient outcomes. Independent of this, it should be recognised that shorter waiting periods are likely to reduce patient anxiety. While these guidelines were developed as part of a proposed framework for consideration by the Victorian Department of Health, they are clinically relevant to national and international cancer services. They are intended to be used by clinical and administrative staff within cancer services. Adoption of these guidelines, which are for the timely triage, review and treatment of cancer patients receiving systemic chemotherapy, aims to ensure that patients receive care within a timeframe that will maximise health outcomes, and that access to care is consistent and equitable across cancer services. Local monitoring of performance against this guideline will enable cancer service providers to manage proactively future service demand.

BACKGROUND The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. METHODS One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. RESULTS The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. CONCLUSIONS p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. Cancer 2016;122:1201–8. © 2016 American Cancer Society.

Purpose Mitomycin C (MMC) plus standard 5-fluorouracil (FU) infusion in weeks 1 and 5 often contributes to radiotherapy interruptions and possibly less-than-ideal outcomes in anal cancer. This study was to evaluate alternative strategies for chemotherapy delivery that might be less toxic or more efficacious, and outcomes of patient-initiated treatment interruption for severe acute toxicity. Materials and methods This was a prospective, nonrandomized study for patients with T1-4N0-3M0 anal squamous carcinoma. Radiotherapy of 54 Gy in 30 fractions over 6 weeks was given with infusion FU 300 mg/m2 /day for 96 hours/week for 6 weeks plus bolus MMC at 10 mg/m2 on D1. Results Fifty patients were recruited (72% female). Median age was 60.5 years (35-84). Forty-seven patients (94%) received 54 Gy. Median duration of chemoradiation was 39 days (37-105). Grade 3 and 4 acute toxicity were observed in 66%. Thirty-one percent with severe acute toxicity developed severe late toxicity. Of those who experienced severe late skin toxicity, 29% did not have severe acute toxicity. Disease-free survival at 5 years was 74% (95% confidence interval [CI], 60-84), and at 9 years 61% (95% CI, 46-74). Overall survival at 5 years was 84% (95% CI, 71-92), and at 9 years 67% (95% CI, 50-81). Colostomy-free survival at 5 years was 70% (95% CI, 56-81), and at 9 years 57% (95% CI, 40-72). Conclusion It is feasible to deliver chemoradiation with bolus MMC and protracted infusion FU for anal cancer. Efficacy and toxicity of this regimen seem similar to conventional chemoradiation with FU/MMC. Acute skin toxicity is not a reliable predictor of severe late skin toxicity.

Background Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer (PRISM) trial evaluated the safety and efficacy of panitumumab as second-line monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Methods This was an open-label, single-arm, multicenter trial that enrolled patients with progressive disease or intolerance to first-line systemic chemotherapy for recurrent or metastatic SCCHN. Patients received panitumumab 9 mg/kg Q3W. The primary endpoint was overall response rate; secondary endpoints included disease control rate, overall survival (OS), progression-free survival (PFS), and safety. Results The overall response rate was 4% (2 of 51 patients) and the disease control rate was 39% (20 of 51 patients). Median PFS was 1.4 months (95% confidence interval [CI] = 1.3–2.4 months). Median OS was 5.1 months (95% CI = 4.3–8.3 months). The most common adverse events were rash/dermatitis acneiform (69%), fatigue (33%), dry skin (21%), and hypomagnesemia (21%). There was one treatment-related death (angioedema). Conclusion Panitumumab monotherapy had limited activity in previously treated patients with recurrent or metastatic SCCHN. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1756–E1761, 2016

Background There is interest in different treatment strategies, including deintensification in good prognosis human papillomavirus-positive (HPV(+)) oropharyngeal squamous cell carcinoma (SCC). We reviewed our experience with weekly cisplatin in low-risk, locoregionally advanced HPV(+) oropharyngeal SCC since late 2009. Methods Data from patients with low-risk HPV(+) oropharyngeal SCC treated with weekly cisplatin (40 mg/m2) and 70 Gy radiotherapy were collected. Low risk was defined as stage III to IV oropharyngeal SCC excluding T1-2N1, T4 or N3 disease, or N2b to N2c disease in patients with >10 pack-year smoking history. Results Of 31 patients, the median age was 56 years (range, 41–69 years). All patients completed 70 Gy radiotherapy within 51 days and 84% completed at least 5 cycles of cisplatin. Grade 3 mucositis occurred in 22 patients (71%) and grade 3 febrile neutropenia in 6 patients (19%). No patients required enteral feeding at 12 months. The median follow-up was 30 months (range, 21–57 months) with no recurrences or deaths. Conclusion Concurrent weekly cisplatin is relatively well-tolerated and associated with excellent disease control in low-risk, locoregionally advanced HPV(+) oropharyngeal SCC. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

The discovery that the human papilloma virus (HPV) is associated with a high and increasing percentage of oropharyngeal squamous cell carcinomas (SCCs) is among the most significant advances in the field of head and neck oncology. HPV-positive oropharyngeal cancer (HPVOPC) has clinical, etiologic, pathologic, and molecular features that distinguish it from HPV-negative disease. Increasingly, HPVOPC is being diagnosed in clinical practice because of the easy availability of p16 immunohistochemistry, a surrogate marker of HPV. The superior prognosis of HPVOPC has led to a reexamination of treatment approaches, and clinical trials are currently investigating strategies to deintensify treatment to reduce acute and late toxicity while preserving efficacy. This is of particular interest in low-risk patients. Unfortunately, patients with HPV-negative tumors still have high rates of locoregional failure and more efficacious treatments are required. This review of oropharyngeal SCC focuses on current and investigational treatment strategies in patients with both HPV-positive and HPV-negative oropharyngeal SCC. Cancer 2014;120:1462–1470. © 2014 American Cancer Society.

Introduction We investigated the relationship between hypoxia, human papillomavirus (HPV) status and outcome in head and neck squamous cell carcinoma. Methods Patients with stage III and IV head and neck squamous cell carcinoma treated on phase I and II chemoradiation trials with 70-Gy radiation combined with tirapazamine/cisplatin or cisplatin/fluorouracil (5FU), hypoxic imaging using [18F]-misonidazole positron emission tomography and known HPV status (by p16 immunohistochemistry) were included in this sub-study. Separate analyses were conducted to consider the impact of tirapazamine on HPV-negative tumours in the phase II trial. Results Both p16-positive oropharyngeal tumours and p16-negative head and neck squamous cell carcinoma tumours had a high prevalence of tumour hypoxia; 14/19 (74%) and 35/44 (80%), respectively. The distribution of hypoxia (primary, nodal) was similar. On phase II, trial patients with p16-negative hypoxic tumours had worse loco-regional control with cisplatin and 5FU compared with tirapazamine and cisplatin (P

CDKN2A (p16) disruption is reported as a frequent event in head and neck squamous cell carcinomas that confers poor prognosis. We investigated the frequency of different potential mechanisms of CDKN2A inactivation in oral tongue squamous cell carcinomas (OTSCC) and their impact on patient outcome. From a cohort of 153 OTSCC patients, 131 formalin fixed paraffin embedded blocks of pre-treatment primary tumours were suitable for further molecular analysis. We assessed CDKN2A (p16) levels by immunohistochemistry (IHC), promoter methylation status by methylation-sensitive high resolution melting, mutation status by Sanger sequencing, gene copy number variation by fluorescence in situ hybridisation, and correlated these with patient outcome. We found that the majority of OTSCC did not overexpress p16 (110/116, 95%), assessed by IHC. The frequency of CDKN2A mutations was 20% (21/103), homozygous loss was 7% (7/97), hemizygous loss 31% (30/97), and promoter methylation was 18% (20/113). We found no evidence of these mechanisms in 24/106 (23%) p16 IHC negative tumours. No significant correlation was identified between any potential mechanism of CDKN2A inactivation and clinical features, including smoking status and age. There was a non-significant trend for worse overall survival for p16 IHC negative patients versus positive patients (HR = 1.81, 95% CI = 0.44-7.47, p = 0.40). No relationship was found between mechanisms of CDKN2A disruption and patient outcome. In conclusion, we demonstrate that CDKN2A alteration is a frequent event in OTSCC tumourigenesis. However, no correlation was identified between different potential mechanisms of CDKN2A disruption and clinical characteristics or patient outcome.

Background The primary purpose of this study was to review the efficacy of unilateral treatment of lateralized tonsil primaries, in particular whether laterality of the primary is a more powerful determinant of contralateral neck failure than advanced ipsilateral nodal classification. Methods A retrospective study of all patients with tonsillar cancer treated with curative intent between January 1990 and December 2002 was performed. Results There were 167 patients, 76% men, median age 58 years, 86% current or ex-smokers. The majority of patients (58%) had stage IV disease. Five-year local, nodal, locoregional, and distant failure rates were 14%, 4%, 18%, and 8%, respectively. Of the 58 patients treated unilaterally, 33% had N2a, N2b, or N3 nodal disease. There were no contralateral nodal failures in the unilaterally treated group. Conclusion These results support the potential use of unilateral radiation therapy (RT) for lateralized tonsil primaries even with advanced ipsilateral nodal disease. © 2013 Wiley Periodicals, Inc. Head Neck 36: 317–322, 2014

Aims Cyclophosphamide was widely used as a single agent prior to the advent of platinum-based regimens for epithelial ovarian cancer, and, in combination with platinum, prior to the adoption of platinum and paclitaxel as standard first-line therapy. As cyclophosphamide currently has no defined role in ovarian cancer we aimed to assess its activity in women with recurrent disease. Methods A retrospective review was conducted of patients from three centers in Melbourne, Australia who had received oral cyclophosphamide treatment for recurrent ovarian cancer. The primary end-point was response rate to oral cyclophosphamide (150 mg p.o. day 1–14) based on Gynecologic Cancer InterGroup (GCIG) CA125 and/or Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary end-points included overall and progression-free survival and toxicity. Results In all, 26 patients were identified and 23 patients were evaluable for response. The median number of prior chemotherapy regimens was three (range 1–6). The response rate to oral cyclophosphamide was 44% with 10 of the 23 patients achieving a partial response (PR) based on GCIG (CA125) criteria. The median number of cycles received was three (range 1–16). Cyclophosphamide showed activity both in patients with platinum-sensitive (seven of 13 PR) and resistant or refractory disease (three of 10 PR). There was no grade 3 or 4 toxicity but two patients ceased cyclophosphamide due to less severe non-hematological toxicity. Conclusion Single agent oral cyclophosphamide is active and well tolerated in recurrent ovarian cancer. Further investigation of oral cyclophosphamide in patients with platinum-sensitive and platinum-resistant disease is warranted.

Introduction To compare nodal response rates following chemoradiotherapy in patients with p16+ and p16− oropharyngeal squamous cell carcinoma (OPSCC). Methods Patients with node-positive OPSCC treated at Peter MacCallum Cancer Centre on the published phase I–III tirapazamine trials were identified. All patients had conventional assessment (clinical examination (CA), CT and/or MRI) and positron emission tomography (PET) at both baseline and 2–4 months post-treatment. Results There were 30 p16+ and 18 p16− patients, the former group having significantly higher stage nodal disease (P = 0.016). The mean overall reduction in nodal size at post-treatment assessment was similar in p16+ and p16− patients (78% vs. 75%), and no statistically significant difference in nodal complete response (CR) rates was detected by either CA (50% vs. 39%, P = 0.35) or PET/PET-CT (93% vs. 83%, P = 0.19). PET was significantly more accurate in determining the true nodal CR rate in both groups, with a negative predictive value of 96%. Conclusion Nodal response rates following chemoradiotherapy appear to be similar in p16+ and p16− patients when assessed by either CA or PET/PET-CT. However, higher nodal CR was seen in PET/PET-CT compared with CA in both groups. Metabolic imaging is more accurate than CA in assessing nodal response post-treatment.

Introduction Definitive treatment with concurrent cisplatin and radiation is the standard of care for locally advanced cervix cancer. The optimal management of patients with a contraindication to cisplatin has not been established. We conducted a retrospective audit of concurrent chemotherapy in a cohort of patients with locally advanced cervix cancer. Methods All patients with locally advanced cervix cancer treated with definitive radiation were entered into a prospective database. Information regarding their demographics, stage, histology, recurrence and survival were recorded. Pharmacy records were reviewed to determine concurrent chemotherapy use. Results A total of 442 patients were included in the audit. Two hundred sixty-nine patients received cisplatin, 59 received carboplatin and 114 received no concurrent chemotherapy. Overall survival was significantly improved with the use of concurrent cisplatin compared with radiation alone (adjusted hazard ratio 0.53, P=0.001), as was disease-free survival and rate of distant failure. The use of carboplatin was not associated with any significant benefit in terms of overall survival or disease-free survival. Conclusion The results of this audit are consistent with the known significant survival benefit with concurrent cisplatin chemotherapy. However, there did not appear to be any significant benefit with carboplatin although there were potential confounding factors. The available evidence in the literature would favour the use of non-platinum chemotherapy rather than carboplatin in patients with contraindications to cisplatin.

Aims: The efficacy of erlotinib (Tarceva, Roche Products, Dee Why, Australia) has been demonstrated in patients with advanced non-small-cell lung cancer (NSCLC). Tarceva lung cancer survival treatment (TRUST) is an open-label, single-arm, phase IV global trial which investigated erlotinib in advanced NSCLC patients who had failed prior therapy or were unsuitable for chemo/radiotherapy. The aim of this analysis was to report the safety and efficacy of erlotinib in the Australian patient subpopulation. Methods: Patients with stage IIIB/IV NSCLC progressing after standard systemic chemotherapy or unsuitable to receive chemo/radiotherapy were eligible for the study. The patients were treated with erlotinib at 150 mg/day orally, until disease progression or unacceptable toxicity. Results: In Australia, 460 patients were recruited. Erlotinib was given as first-line (16%), second-line (49%) or third-line (35%) treatment. In the intent-to-treat population (N = 460), the median progression-free survival was 2.7 months (95% CI 2.3–3.4), 1-year survival was 35% (95% CI 30–39%) and median overall survival was 6.9 months (95% CI 5.7–8.0). Tumor response rates were available for 363 patients, with a disease control rate of 58%. Of the 460 patients included in the safety analysis, 24% had one or more erlotinib-related adverse event (AE). Rash was reported in 77% of patients, most commonly grade 1/2 (63%). Treatment-related serious AE were reported in 7% of patients; most commonly diarrhea (2%). Dose modifications were required in 18% of patients. Conclusions: Outcomes for Australian patients confirmed the efficacy and tolerability of erlotinib for the treatment of advanced NSCLC in routine clinical practice.

Introduction: The aim of this study was to evaluate the impact of positron emission tomography/computerised tomography (PET/CT) as an adjunct to conventional imaging (CI) in the management of nasopharyngeal cancer (NPC) both for initial staging and assessment of post-treatment response. Methods: All NPC cases referred to the Peter MacCallum Centre for Metabolic Imaging between January 2002 and December 2007 were identified. In patients undergoing initial staging, any differences between the pre-PET/CT management plan based on CI and that following performance of the PET/CT scan were noted. Clinical impact was scored using the Centre's published criteria: 'high' if PET/CT changed the primary treatment modality or intent, ‘medium’ if treatment modality was unchanged but the radiotherapy technique or dose was altered, and ‘low’ if there was no change in treatment modality or intent. Patients undergoing PET/CT following definitive treatment were scored according to whether or not they achieved a complete metabolic response. Results: Forty-eight patients underwent a staging PET/CT. The clinical impact was high in 8%, medium in 25% and low in 66% of patients. Twenty-one patients were scanned for post-treatment response. PET/CT was less frequently equivocal than MRI (3 vs 8/21). A complete metabolic response on PET/CT was associated with a 93% negative predictive value for subsequent recurrence. Conclusion: PET/CT is a valuable staging tool for the detection of occult metastatic disease and defining the extent of neck nodal disease. Post-treatment, a complete metabolic response on PET/CT has a very high negative predictive value with fewer equivocal results than MRI.

Introduction: The objective of this paper was to review the results of primary non-surgical treatment with the aim of larynx preservation for loco-regionally advanced larynx cancer (LALC). Methods: All patients with LALC presenting between January 2002 and December 2006 who were selected for primary non-surgical treatment were included in this study. Results: There were 60 patients, 48% with stage III and 52% with stage IV disease. The median follow-up of living patients was 41 months. Larynx preservation with local disease control was achieved in 83% and 77% of patients at 3 and 5 years, respectively. Failure-free survival at 3 and 5 years was 66% and 59%, respectively, and overall survival was 67% and 45%, respectively. All patients with larynx preservation had a functional voice. Two patients became feeding tube dependant. Thirty-nine percent of all deaths were unrelated to LALC. Conclusions: Primary non-surgical treatment achieves high rates of larynx preservation with a low rate of severe complications but overall survival remains disappointing.

Background/Aims: Optimal delivery of intraperitoneal (IP) chemotherapy is dependent on adequate drug distribution. An accurate understanding of the limitations of IP distribution is critical if we are to improve cytotoxic delivery through this route. Methods: Using repeated scintigraphic peritoneography we investigated peritoneal fluid distribution in patients receiving IP therapy. Both early (1–6 h) and late (24–48 h) images were performed. The peritoneal cavity was divided into six regions; pouch of Douglas, left and right paracolic gutters, left and right subphrenic spaces and the right subhepatic space. The distribution in each region was classified as absent (0), faint (1) or intense (2). A total distribution score was calculated from the summation of distribution values for each of the six regions. Distribution was then graded according to the total distribution score as follows: Grade 0 = 0–3; Grade 1 = 4–6; Grade 2 = 7–9; and Grade 3 = 10–12. Results: Twenty-six participants were included in the study: all 26 patients had early imaging performed and 21 of these also had late imaging. Thirteen (50%) and 15 (71%) patients had grade 1 or 2 IP distribution on early and late imaging respectively. The most common abdominal regions to show maldistribution were the subphrenic spaces. Conclusions: This study highlights the deficiencies of distribution following IP drug delivery, with the majority of patients demonstrating multiple regions of faint or absent uptake on scintigraphic peritoneography imaging. Future large clinical studies investigating IP chemotherapy should include analyses of IP distribution to improve our understanding of optimal drug delivery through this route.

Percutaneous endoscopic gastrostomy (PEG) tubes have largely replaced nasogastric tubes (NGT) for nutritional support of patients with head and neck cancer undergoing curative (chemo)radiotherapy without any good scientific basis. A randomized trial was conducted to compare PEG tubes and NGT in terms of nutritional outcomes, complications, patient satisfaction and cost. The study was closed early because of poor accrual, predominantly due to patients' reluctance to be randomized. There were 33 patients eligible for analysis. Nutritional support with both tubes was good. There were no significant differences in overall complication rates, chest infection rates or in patients' assessment of their overall quality of life. The cost of a PEG tube was 10 times that of an NGT. The duration of use of PEG tubes was significantly longer, a median 139 days compared with a median 66 days for NGT. We found no evidence to support the routine use of PEG tubes over NGT in this patient group.

Background. The aim of this study was to deter- mine the incidence of isolated nodal failure in patients with N2/3 disease who achieved a complete clinical and radiological response (CR) at 12 weeks postchemoradiation, when no planned neck dissection was performed. Methods. We analyzed the nodal response and subsequent neck control of 102 patients with initial N2/3 disease treated on the Trans Tasman Radiation Oncology Group 98.02 study. Results. With a median 4.3 years follow-up, the patterns of first failure in the CR patients were local 4%, local and nodal 2%, distant 28%, and locoregional plus distant (within 1 month) 6%.There were no patients who had only neck failure. Conclusion. Patients in this trial with N2/3 disease who obtained a clinical and radiological complete response to che- moradiation had a zero incidence of isolated neck failure without a planned neck dissection. The continued use of planned neck dissections in this patient subset cannot be justified. V C 2008

This study evaluates the utility of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with a node-positive mucosal head and neck squamous cell carcinoma who achieved a complete response at the primary site but had a residual mass in the neck 8 weeks or more after definitive (chemo)radiotherapy.Between October 1996 and July 2002, 39 eligible patients were identified. The reference PET scan was performed at a median of 12 weeks (range, 8-32 weeks) after treatment.PET showed no metabolic activity in the residual mass in 32 patients. Five of these patients had a neck dissection and were all pathologically negative. The remaining 27 patients were observed for a median of 34 months (range, 16-86 months), with only one locoregional failure. The negative predictive value of PET for viable disease in a residual anatomic abnormality was 97%.Patients who have achieved a complete response at the primary site but have a residual abnormality in the neck that is PET negative approximately 12 weeks after treatment do not require neck dissection and can be safely observed. Head Neck

Intensity-modulated radiotherapy (IMRT) has been available at Peter MaCallum Cancer Centre (PMCC) since November 2000. The present report illustrates two cases of our early experience with IMRT. Case 1 is a 66-year-old man with a T(1)N(2)M(0) nasopharyngeal carcinoma treated with chemo-radiotherapy using parotid-sparing IMRT. Fourteen months following treatment he remains in complete remission, with salivary function assessed using a xerostomia-specific quality of life questionnaire, having returned to near pretreatment levels by 12 months. Case 2 is a 70-year-old man with a T(4)N(0)M(0) base of tongue squamous cell carcinoma treated with chemo-radiotherapy after refusing radical surgery. He had received subtotal nodal irradiation to 36 Gy in 1994 for Hodgkins disease stage IIA. A radical dose was still achievable despite previous irradiation without exceeding unacceptable spinal cord dose with IMRT. He remains in complete remission 14 months from his initial presentation without evidence of neurological toxicity. Intensity-modulated radiotherapy allows sparing of critical normal structures in the head and neck without compromising dose to the tumour. It is, therefore, desirable for several clinical applications and essential in some, if unacceptable compromises are not to be made.

Background. Residual structural abnormalities af- ter definitive treatment of head and neck squamous cell car- cinoma (HNSCC) are common and pose difficult management problems. The usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) to supplement con- ventional evaluation with clinical and standard radiologic exam- ination (CE) in such patients was assessed. Methods. Fifty-three eligible patients were identified with residual structural abnormalities on CE. True disease extent could be validated in 46 patients. Patients had a median potential follow-up of 55 months (range, 41-75 months) from the date of PET scan to the analysis closeout date. Results. PET had better diagnostic accuracy than CE (p = .0002) and induced management change in 21 patients (40%; 95% confidence interval (CI), 26%-54%), including avoid- ance of unnecessary planned surgery in 14 patients with neg- ative PET. Appropriate management change was confirmed in 19 (95%) of 20 evaluable cases. Disease presence and ex- tent assessment by PET were significant predictors of survival (p < .0001), whereas the extent of disease determined by CE was not. Conclusion. PET added significantly to the value of CE in restaging disease in patients with structural abnormalities after definitive treatment of HNSCC. Management decisions based on PET were appropriate in most patients. A 2004 Wiley Periodicals, Inc. Head Neck 26: 1008-1017, 2004

Background. Sinonasal undifferentiated carcino- ma (SNUC) is an uncommon malignancy associated with poor prognosis. The optimal treatment approach for SNUC has not been established was performed. Methods. A retrospective review of all patients with SNUC seenatthePeterMacCallumCancerCentreovera12-yearperiod. Results. Ten patients with SNUC were identified, with nine having locally advanced disease (T4). Seven were treated with three cycles of platinum and 5-fluorouracil followed by radiation with two cycles of concurrent platinum. In these seven patients, the 2-year progress on-free survival was 43% (95% CI, 11% to 82%) and the 2-year overall survival was 64% (95% CI, 23% to 91%). One patient with a T1N0 nasal cavity tumor treated with radiation alone has not had a relapse. Two patients who were treated with initial surgical resection, prior to referral to our institution, received postoperative radiation, but they subse- quently had relapses and died. Conclusion. Induction chemotherapy followed by concur- rent chemoradiation is a promising treatment strategy for SNUC. A 2004 Wiley Periodicals, Inc. Head Neck 26: 435-441, 2004

The purpose of this study was to evaluate the local control, pattern of recurrence, overall survival, and prognostic factors of patients with squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma of the paranasal sinuses (PNS) and nasal cavity (NC) presenting to our center for curative treatment over a 10-year period.Between 1991 and 2000, 60 patients with SCC (n = 32), adenocarcinoma (n = 25), and undifferentiated carcinoma (n = 3) of the PNS or NC were identified. Forty patients received surgery and postoperative radiotherapy, four surgery alone; 11, radiotherapy alone; three radical radiotherapy after surgical recurrence; one, chemoradiotherapy and surgery; and one, induction chemotherapy followed by radiotherapy.Forty-seven patients (78%) were seen with T3-4 disease; however, most (92%) were node negative on initial assessment. The predominant failure pattern was local disease persistence or recurrence. The estimated 2- and 5-year local control rates were 63% and 49%, respectively. Orbital and neural invasion significantly affected local control. The estimated 2- and 5 year overall survival rates were 57% and 40%, respectively.Local failure remains the dominant cause for poor outcome in this group of patients. Because of the proximity of critical normal structures, the ability to perform adequate surgery and to deliver effective radiotherapy is limited in many cases. The use of postoperative concurrent chemoradiotherapy warrants further investigation.

A prospective study was undertaken to evaluate a policy of selective, single-modality elective neck treatment in T1-2, node-negative oral tongue squamous cell carcinoma.Where the primary tumor showed 1 of the 4 key pathological criteria (greater than 7 mm of muscle invasion, less than 5 mm of resection margin, perineural or lymphovascular invasion), radiotherapy was delivered to the primary site and the at-risk undissected neck. Otherwise patients underwent ipsilateral neck dissection within 4 weeks of initial resection. Prospective quality of life assessments were performed.The study was closed after accrual of 25 patients, because the high locoregional recurrence rate met early stopping criteria. With a median follow-up of 3.4 years, the locoregional recurrence rate was 23%. The 4-year overall and disease-free survival rates were 71% and 64%, respectively.The poor disease-free survival reflects the need for better prognostic markers and more aggressive treatment in these patients.

Twenty-two patients with malignant pericardial effusions were treated with subxiphoid partial pericardiectomy between 1984 and 1989. Thirteen patients also had a sclerosing agent instilled intrapericardially. Tamponade was relieved by pericardiocentesis before administration of general anesthesia. In 18 patients (82%), the effusions were controlled for longer than 30 days, and two patients died before 30 days without effusion. There were two recurrences at 1.5 and 7 months. There was one death due to hemorrhage from a laceration in a heavily infiltrated pericardium, and one patient had persistent dyspnea after the procedure. Complications included transient atrial arrhythmias (two patients), chest pain after sclerosant instillation (three patients), and fever greater than 37.5 degrees C after sclerosant (five patients). The survival range was 0.1 to 18 months (median, 5 months). Subxiphoid partial pericardiectomy with or without intrapericardial sclerosant is a safe and efficacious treatment for malignant pericardial effusions.