Tsien Fua

Efficacy of low dose radiotherapy for primary orbital marginal zone lymphoma

Abstract Marginal zone lymphoma (MZL) is a radiosensitive tumor, with high local control (LC) rates with moderate dose radiotherapy (RT). This retrospective study, performed at the Peter MacCallum Cancer Centre, evaluated the efficacy and toxicity of patients with orbital MZL treated to 24–25 Gy. Twenty-four patients (27 orbits) were identified, with median follow-up of 41 months. Disease was conjunctival in 16 orbits (59%), lacrimal in seven (26%), in the eyelid in one (4%) and elsewhere in three (11%). All patients attained a complete response. Three patients had treatment failures: one local relapse, one contralateral and one distant relapse. Freedom from local failure, freedom from progression, progression-free survival and overall survival were 100%, 90%, 90% and 100% at 2 years and 92%, 81%, 81% and 100% at 5 years, respectively. Aside from cataractogenesis, there was no significant late toxicity. Our study shows that RT doses of 24–25 Gy provide high rates of LC for orbital MZL with acceptable morbidity.

Incorporating Quantitative Single Photon Emission Computed Tomography into Radiation Therapy Treatment Planning for Lung Cancer: Impact of Attenuation and Scatter Correction on the Single Photon Emission Computed Tomography–Weighted Mean Dose and Functional Lung Segmentation

PURPOSE To assess the impact of attenuation and scatter corrections on the calculation of single photon emission computed tomography (SPECT)-weighted mean dose (SWMD) and functional volume segmentation as applied to radiation therapy treatment planning for lung cancer. METHODS AND MATERIALS Nine patients with lung cancer underwent a SPECT lung perfusion scan. For each scan, four image sets were reconstructed using the ordered subsets expectation maximization method with attenuation and scatter corrections ranging from none to a most comprehensive combination of attenuation corrections and direct scatter modeling. Functional volumes were segmented in each reconstructed image using 10%, 20%, …, 90% of maximum SPECT intensity as a threshold. Systematic effects of SPECT reconstruction methods on treatment planning using functional volume were studied by calculating size and spatial agreements of functional volumes, and V(20) for functional volume from actual treatment plans. The SWMD was calculated for radiation beams with a variety of possible gantry angles and field sizes. RESULTS Functional volume segmentation is sensitive to the particular method of SPECT reconstruction used. Large variations in functional volumes, as high as >50%, were observed in SPECT images reconstructed with different attenuation/scatter corrections. However, SWMD was less sensitive to the type of scatter corrections. SWMD was consistent within 2% for all reconstructions as long as computed tomography-based attenuation correction was used. CONCLUSION When using perfusion SPECT images during treatment planning optimization/evaluation, the SWMD may be the preferred figure of merit, as it is less affected by reconstruction technique, compared with threshold-based functional volume segmentation.

Weekly cisplatin and radiotherapy for low risk, locoregionally advanced human papillomavirus–positive oropharyngeal squamous cell carcinoma

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.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.

Phase 3 trial of domiciliary humidification to mitigate acute mucosal toxicity during radiation therapy for head-and-neck cancer: first report of Trans Tasman Radiation Oncology Group (TROG) 07.03 RadioHUM study.

PURPOSE To assess the impact of domicile-based humidification on symptom burden during radiation therapy (RT) for head-and-neck (H&N) cancer. METHODS AND MATERIALS From June 2007 through June 2011, 210 patients with H&N cancer receiving RT were randomized to either a control arm or to receive humidification using the Fisher & Paykel Healthcare MR880 humidifier. Humidification commenced on day 1 of RT and continued until Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, clinical mucositis (CMuc) grade ≤1 occurred. Forty-three patients (42%) met a defined benchmark for humidification compliance and contributed to per protocol (PP) analysis. Acute toxicities, hospitalizations, and feeding tube events were recorded prospectively. The McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) was used for patient-reported outcomes. The primary endpoint was area under the curve (AUC) for CMuc grade ≥2. RESULTS There were no significant differences in AUC for CMuc ≥2 between the 2 arms. Humidification patients had significantly fewer days in hospital (P=.017). In compliant PP patients, the AUC for CTCAE functional mucositis score (FMuc) ≥2 was significantly reduced (P=.009), and the proportion who never required a feeding tube was significantly greater (P=.04). HNRQ PP analysis estimates also in the direction favoring humidification with less symptom severity, although differences at most time points did not reach significance. CONCLUSIONS TROG 07.03 has provided efficacy signals consistent with a role for humidification in reducing symptom burden from mucositis, but the influence of humidification compliance on the results moderates recommendations regarding its practical utility.

Prognostic Significance of PD-L1 and CD8 Immune Cells in HPV Oropharyngeal Squamous Cell Carcinoma.

Assessment of CD8+ cell infiltration and PD-L1 expression on intratumoral immune cells identified a subgroup of HPV+ OPSCC patients with excellent clinical outcomes. Immunophenotyping tumors provided prognostic information beyond that provided by existing TNM-based staging systems. Human papilloma virus–positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) represents a distinct subgroup of head and neck cancers associated with clinical outcomes that are not accurately categorized by existing tumor–node–metastasis-based staging methods. Given the significant impact of immune parameters, such as tumor-infiltrating lymphocytes (TIL) in many cancers, we sought to determine if immunophenotyping tumors can improve categorization of HPV+ OPSCCs for prognostic purposes. In a cohort of 190 patients with HPV+ OPSCC, we quantified and determined the localization of CD8+ TILs, as well as PD-L1–expressing tumor cells (TC) and immune cells (IC). The prognostic significance of these parameters on overall survival (OS) was evaluated, and their contribution to existing prognostic models was determined. High CD8+ TIL abundance (≥30% on stromal or intratumoral ICs) was seen in 61.3% patients and was associated with improved OS [HR, 0.4; 95% confidence interval (CI), 0.2–0.9; P = 0.017]. Although the expression of PD-L1 on TC was not prognostic, high expression of PD-L1 on ≥5% of intratumoral ICs was found in 38.5% patients and was significantly associated with improved OS (HR, 0.37; 95% CI, 0.15–0.93; P = 0. 023). Both high intratumoral IC PD-L1 expression and abundant CD8+ TILs in HPV+ OPSCCs identify subgroups of patients with excellent outcomes and provide additional prognostic information beyond existing staging systems. Cancer Immunol Res; 6(3); 295–304. ©2018 AACR.

Transoral robotic surgery: implementation as a tool in head and neck surgery - a single-centre Australian experience.

Transoral robotic surgery (TORS) is now a well‐validated technique for resection of head and neck cancers. Benefits include reduced patient morbidity, swallowing preservation and rationalization of adjuvant therapies.

Non-smoking, non-drinking elderly females, a 5 year follow-up of a clinically distinct cohort of oral squamous cell carcinoma patients

To examine differences in survival and clinical outcomes of elderly patients without traditional risk factors presenting with oral squamous cell carcinoma. Retrospective review of 287 consecutive patients divided into 2 treatment period cohorts treated for oral SCC between the 1st Jan 2007 and 31st Dec 2012. Patients were classified as either smoker-drinkers (SD) or non-smoking, non-drinking (NSND). Only patients with oral sub-site primaries according to ICD-10 were included. Carcinomas of the lip, tonsil, base of tongue and oro-pharyngeal subsites were excluded. Of the study population (N = 287), 24.4% were NSND and 9.75% were NSND elderly (older than 70 years) females. >50% of tumours arose from the oral tongue in NSND patients (p = 0.022) and there was a higher rate of recurrent and persistent disease (42.9% vs 27.6%, p = 0.005). Disease specific survival at 5 years was significantly reduced when NSND elderly females were compared to all other patients (p < 0.001) as well as age matched controls (p = 0.006). This effect was verified independently in each cohort.The results of this study suggest that NSND elderly females are a distinct patient population with poorer disease specific survival outcomes.

Unilateral radiotherapy treatment for p16/human papillomavirus-positive squamous cell carcinoma of unknown primary in the head and neck: Radiotherapy for p16 + Unknown Primary

The outcomes of unilateral radiotherapy treatment for patients with p16/HPV‐positive squamous cell carcinomas of unknown primary (SCCUP) affecting cervical lymph nodes are under‐reported. Compared to radiating large volumes of the pharyngeal axis (the more common approach), this is potentially a much less toxic treatment for a good prognosis group.

A systematic review of the impact of outpatient clinical pharmacy services on medication-related outcomes in patients receiving anticancer therapies:

Background Patients receiving anticancer therapies are frequently prescribed complex and high-risk medication regimens, which at times can result in medication misadventures. The objective of this review was to assess the effect of outpatient clinical pharmacy services on medication-related outcomes in patients receiving anticancer therapies, including patients undergoing radiotherapy. Methods A systematic review of original publications indexed in EMBASE, MEDLINE and Cochrane Library from June 2007 to June 2017. Eligible studies evaluated outpatient pharmacy clinic services for cancer patients and reported at least one medication-related quantitative outcome measure. Two authors independently reviewed full-text articles for inclusion, then extracted data and performed quality and risk of bias assessments. Results Of 908 identified publications, 13 met predefined eligibility criteria; 1 randomised control trial, 2 controlled cohort studies and 10 uncontrolled before–after studies. Many excluded studies described outpatient pharmacy services but lacked medication-related outcomes. All included studies had informative practice model designs, with interventions for drug-related problems including drug dose optimisation (n = 8), reduced drug interaction (n = 6) and adverse drug reaction reporting (n = 3). Most studies (n = 11) reported on symptom improvement, commonly nausea (n = 7) and pain (n = 5). Of four studies in radiotherapy cohorts, pharmacist involvement was associated with improved symptoms, satisfaction and wellbeing scores. Conclusion Few studies have objectively assessed outpatient pharmacy cancer services, even fewer in the radiotherapy settings. Although the results support these services, significant heterogeneity and bias in the study designs prohibit robust conclusions and further controlled trials are required.

Weekly cisplatin and radiotherapy for low risk, locoregionally advanced human papillomavirus-positive oropharyngeal squamous cell carcinoma: Weekly Cisplatin and RT in HPV(+) OP SCC

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.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.