Patient-Reported Symptom Severity, Health-Related Quality of Life, and Emotional Distress Trajectories During and After Radiation Therapy for Human Papillomavirus-Associated Oropharyngeal Cancer: A TROG 12.01 Secondary Analysis.

PURPOSE: This secondary analysis of clinical trial TROG 12.01, involving patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma, aimed to identify patient-reported outcome (PRO) trajectories before, during, and after chemoradiotherapy. METHODS AND MATERIALS: Head and neck cancer symptom severity (HNSS) and interference (HNSI), generic health-related quality of life (HRQL), and emotional distress were assessed with the MD Anderson Symptom Inventory-Head and Neck, Functional Assessment of Cancer Therapy-General, and Hospital Anxiety and Depression Scale questionnaires, respectively. Latent class growth mixture modeling (LCGMM) was used to identify distinct underlying trajectories. Baseline and treatment variables were compared between trajectory groups. RESULTS: The LCGMM identified latent trajectories for all PROs: HNSS, HNSI, HRQL, anxiety, and depression. Four HNSS trajectories (HNSS1-4) were identified, distinguished by differences in HNSS at baseline, during the peak of treatment symptoms, and during early and intermediate recovery. All trajectories were stable beyond 12 months. The reference trajectory (HNSS4, n = 74) score was 0.1 (95% confidence interval [CI], 0.1-0.2) at baseline, peaking at 4.6 (95% CI, 4.2-5.0), with rapid early recovery (1.1; 95% CI, 0.8-2.2) and gradual improvement to 12 months (0.6; 95% CI, 0.5-0.8). Patients in HNSS2 (high baseline, n = 30) reported higher baseline scores (1.4; 95% CI, 0.8-2.0) but were otherwise similar to HNSS4. Patients in HNSS3 (low acute, n = 53) reported reduced acute symptoms (2.5; 95% CI, 2.2-2.9) with stable scores beyond 9 weeks after chemoradiotherapy (1.1; 95% CI, 0.9-1.4). Patients in HNSS1 (slow recovery, n = 25) had slower recovery from an acute peak of 4.9 (95% CI, 4.3-5.6) to 0.9 (95% CI, 0.6-1.3) at 12 months. Age, performance status, education, receipt of cetuximab, and baseline anxiety varied between trajectories. The other PRO models demonstrated clinically relevant trajectories, with distinct associations with baseline factors. CONCLUSIONS: LCGMM identified distinct PRO trajectories during and after chemoradiotherapy. These and their associations with variations in the characteristics and treatment factors of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma provide clinically relevant insights into identifying patients who may require increased support before, during, or after chemoradiotherapy.

Structure-Enantioselectivity Relationship (SER) Study of Cinchona Alkaloid Chlorocyclization Catalysts.

Various structural elements of the Cinchona alkaloid dimers are interrogated to establish a structure-enantioselectivity relationship (SER) in three different halocyclization reactions. SER for chlorocyclizations of a 1,1-disubstituted alkenoic acid, a 1,1-disubstituted alkeneamide, and a trans-1,2-disubstituted alkeneamide showed variable sensitivities to linker rigidity and polarity, aspects of the alkaloid structure, and the presence of two or only one alkaloid side group defining the catalyst pocket. The conformational rigidity of the linker-ether connections was probed via DFT calculations on the methoxylated models, uncovering especially high barriers to ether rotation out of plane in the arene systems that include the pyridazine ring. These linkers are also found in the catalysts with the highest enantioinduction. The diversity of the SER results suggested that the three apparently analogous test reactions may proceed by significantly different mechanisms. Based on these findings, a stripped-down analogue of (DHQD)2PYDZ, termed "(trunc)2PYDZ", was designed, synthesized, and evaluated, showing modest but considerable asymmetric induction in the three test reactions, with the best performance on the 1,1-disubstituted alkeneamide cyclization. This first effort to map out the factors essential to effective stereocontrol and reaction promotion offers guidance for the simplified design and systematic refinement of new, selective organocatalysts.

Patient- and Clinician-Reported Outcomes in Human Papillomavirus-Associated Tonsillar Carcinoma Treated With Unilateral and Bilateral Intensity Modulated Radiation Therapy-A Substudy From TROG 12.01.

PURPOSE: The aim of this TROG 12.01 substudy was to report longitudinal variations in patient- (PRO) and clinician-reported outcomes based on receipt of unilateral (URT) or bilateral radiation therapy (BRT). METHODS AND MATERIALS: Patients with lateralized T1-2 N1-2b human papillomavirus-associated tonsillar carcinoma (AJCC7) enrolled on TROG 12.01 were eligible. The primary endpoint was patient-reported radiation symptom severity score (MDASI-RSS) at 2 years, a composite of 9 MDASI-Head and Neck (HN) symptom items. Secondary endpoints included patient-reported symptom burden and interference (MDASI-HN), quality of life (FACT-HN), emotional distress (HADS), return to work (RTW), clinician-reported performance status scale (PSS-HN), and late adverse events (CTCAE). Mean MDASI-RSS, symptom severity (MDASI-SS), symptom interference (MDASI-SI) and selected single items were compared 1 week, 3 months, and 2 years post-RT. RESULTS: Seventy-four patients were eligible for analysis (26 URT, 48 BRT). Median follow-up was 3.7 years (1.8-5.2 years). Sociodemographic, staging, and treatment variables were mostly balanced, with larger primaries observed in the BRT group. Four regional failures were reported (3 URT, 1 BRT), including one isolated contralateral regional failure in the URT cohort. Mean MDASI-RSS scores did not differ at 2 years (URT vs BRT, 1.1 vs 1.3; difference 0.1 [95% CI: -0.7 to 0.9], P = .75) or at any other time points for the MDASI-RSS, MDASI-SS, and MDASI-SI scores, except for worse MDASI-SI 1 week after treatment in the BRT group (4.7 vs 5.6). Fatigue (6.6 vs 5.4) at 1 week and dry mouth (3.5 vs 2.0) at 2 years were also worse in the BRT group. FACT-HN, HADS, RTW, PSS-HN, and CTCAE results were similar across the follow-up period. CONCLUSIONS: In this favorable-risk cohort, treatment laterality resulted in fewer differences than anticipated in patient-reported or clinician-reported outcomes. Two years after treatment patients treated with BRT reported significantly worse dry mouth. Longer follow-up is needed to determine the impact of treatment laterality on late effects.

Infrared quantification of ethanol and 1-butanol hydrogen bonded hydroxyl distributions in cyclohexane.

Quantifying the mid-range infrared hydroxyl stretch absorbance region has traditionally been a challenge due to the wavenumber dependence of the attenuation coefficient. Interpretation often assigns a single attenuation coefficient to each type of hydrogen-bonded aggregate. This work leverages a recently developed technique of scaling hydroxyl stretching absorbances in the mid-infrared region with a continuous attenuation coefficient function that produces integrated areas which directly correlate to hydroxyl concentrations. After scaling, the hydroxyl absorbance is fitted with five curves, of which four are dominant. These four curves represent unique hydroxyl configurations and translate to specific aggregate structures. The technique is applied to ethanol and 1-butanol. The resulting population distributions of hydrogen-bonded hydroxyl configurations are compared with the resummed thermodynamic perturbation theory (RTPT) model for linear chains as a function of concentration and temperature. The model is demonstrated to capture the critical features of the distributions.

Skeletal Ni electrode-catalyzed C-O cleavage of diaryl ethers entails direct elimination via benzyne intermediates.

Diaryl ethers undergo electrocatalytic hydrogenolysis (ECH) over skeletal Ni cathodes in a mild, aqueous process that achieves direct C-O cleavage without initial benzene ring saturation. Mechanistic studies find that aryl phenyl ethers with a single para or meta functional group (methyl, methoxy, or hydroxy) are selectively cleaved to the substituted benzene and phenol, in contrast to recently reported homogeneous catalytic cleavage processes. Ortho positioning of substituents reverses this C-O bond selectivity, except for the 2-phenoxyphenol case. Together with isotope labeling and co-solvent studies, these results point to two distinct cleavage mechanisms: (a) dual-ring coordination and C-H activation, leading to vicinal elimination to form phenol and a surface-bound aryne intermediate which is then hydrogenated and released as the arene; and (b) surface binding in keto form by the phenolic ring of the hydroxy-substituted substrates, followed by direct displacement of the departing phenol. Notably, acetone inhibits the well-known reduction of phenol to cyclohexanol, affording control of product ring saturation. A byproduct of this work is the discovery that the ECH treatment completely defluorinates substrates bearing aromatic C-F and C-CF3 groupings.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Intramolecular Relaxation Dynamics Mediated by Solvent-Solute Interactions of Substituted Fluorene Derivatives. Solute Structural Dependence.

Several fluorene derivatives exhibit excited-state reactivity and relaxation dynamics that remain to be understood fully. We report here the spectral relaxation dynamics of two fluorene derivatives to evaluate the role of structural modification in the intramolecular relaxation dynamics and intermolecular interactions that characterize this family of chromophores. We have examined the time-resolved spectral relaxation dynamics of two compounds, NCy-FR0 and MK-FR0, in protic and aprotic solvents using steady-state and time-resolved emission spectroscopy and quantum chemical computations. Both compounds exhibit spectral relaxation characteristics similar to those seen in FR0, indicating that hydrogen bonding interactions between the chromophore and solvent protons play a significant role in determining the relaxation pathways available to three excited electronic states.

Excited-State Dynamics of a Substituted Fluorene Derivative. The Central Role of Hydrogen Bonding Interactions with the Solvent.

Substituted fluorene structures have demonstrated unusual photochemical properties. Previous reports on the substituted fluorene Schiff base FR0-SB demonstrated super photobase behavior with a ΔpKb of ∼14 upon photoexcitation. In an effort to understand the basis for this unusual behavior, we have examined the electronic structure and relaxation dynamics of the structural precursor of FR0-SB, the aldehyde FR0, in protic and aprotic solvents using time-resolved fluorescence spectroscopy and quantum chemical calculations. The calculations show three excited singlet states in relatively close energetic proximity. The spectroscopic data are consistent with relaxation dynamics from these electronic states that depend on the presence and concentration of solvent hydroxyl functionality. These results underscore the central role of solvent hydrogen bonding to the FR0 aldehyde oxygen in mediating the relaxation dynamics within this molecule.

Femtosecond dynamics and coherence of ionic retro-Diels-Alder reactions.

Ultrafast tunnel ionization enables femtosecond time-resolved dynamic measurements of the retro-Diels-Alder reactions of positively charged cyclohexene, norbornene, and dicyclopentadiene. Unlike the reaction times of 500-600 ps that are observed following UV excitation of neutral species, on the ionic potential energy surfaces, these reactions occur on a single picosecond timescale and, in some cases, exhibit vibrational coherence. In the case of norbornene, a 270 cm-1 vibrational mode is found to modulate the retro-Diels-Alder reaction.

Randomized Trial of Radiation Therapy With Weekly Cisplatin or Cetuximab in Low-Risk HPV-Associated Oropharyngeal Cancer (TROG 12.01) - A Trans-Tasman Radiation Oncology Group Study.

PURPOSE: The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin. METHODS AND MATERIALS: TROG12.01, a randomized, multicenter trial involving 15 sites in Australia and New Zealand enrolled patients with HPV-associated oropharyngeal squamous cell carcinoma, American Joint Committee on Cancer 7th edition stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomized (1:1) to receive radiation therapy (70 Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40 mg/m2, or cetuximab, loading dose of 400 mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks postcompletion of radiation therapy using the area under the curve. Trial was registered on ClinicalTrials.gov: NCT01855451. RESULTS: Between June 17, 2013, and June 7, 2018, 189 patients were enrolled, with 92 in cisplatin arm and 90 in cetuximab included in the main analysis. There was no difference in the primary endpoint of symptom severity; difference in area under the curve cetuximab-cisplatin was 0.05 (95% confidence interval [CI], -0.19, 0.30), P = .66. The T-score (mean number of ≥grade 3 acute adverse events) was 4.35 (standard deviation 2.48) in the cisplatin arm and 3.82 (standard deviation 1.8) in the cetuximab arm, P = .108. The 3-year failure-free survival rates were 93% (95% CI, 86%-97%) in the cisplatin arm and 80% (95% CI, 70%-87%) in the cetuximab arm (hazard ratio = 3.0 [95% CI, 1.2-7.7]); P = .015. CONCLUSIONS: For patients with low-risk HPV-associated oropharyngeal cancer, radiation therapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared with radiation therapy and weekly cisplatin. Radiation therapy and cisplatin remain the standard of care.

Isoenergetic two-photon excitation enhances solvent-to-solute excited-state proton transfer.

Two-photon excitation (TPE) is an attractive means for controlling chemistry in both space and time. Since isoenergetic one- and two-photon excitations (OPE and TPE) in non-centrosymmetric molecules are allowed to reach the same excited state, it is usually assumed that they produce similar excited-state reactivity. We compare the solvent-to-solute excited-state proton transfer of the super photobase FR0-SB following isoenergetic OPE and TPE. We find up to 62% increased reactivity following TPE compared to OPE. From steady-state spectroscopy, we rule out the involvement of different excited states and find that OPE and TPE spectra are identical in non-polar solvents but not in polar ones. We propose that differences in the matrix elements that contribute to the two-photon absorption cross sections lead to the observed enhanced isoenergetic reactivity, consistent with the predictions of our high-level coupled-cluster-based computational protocol. We find that polar solvent configurations favor greater dipole moment change between ground and excited states, which enters the probability for TPE as the absolute value squared. This, in turn, causes a difference in the Franck-Condon region reached via TPE compared to OPE. We conclude that a new method has been found for controlling chemical reactivity via the matrix elements that affect two-photon cross sections, which may be of great utility for spatial and temporal precision chemistry.

Steric effects in light-induced solvent proton abstraction.

The significance of solvent structural factors in the excited-state proton transfer (ESPT) reactions of Schiff bases with alcohols is reported here. We use the super photobase FR0-SB and a series of primary, secondary, and tertiary alcohol solvents to illustrate the steric issues associated with solvent to photobase proton transfer. Steady-state and time-resolved fluorescence data show that ESPT occurs readily for primary alcohols, with a probability proportional to the relative -OH concentration. For secondary alcohols, ESPT is greatly diminished, consistent with the barrier heights obtained using quantum chemistry calculations. ESPT is not observed in the tertiary alcohol. We explain ESPT using a model involving an intermediate hydrogen-bonded complex where the proton is "shared" by the Schiff base and the alcohol. The formation of this complex depends on the ability of the alcohol solvent to achieve spatial proximity to and alignment with the FR0-SB* imine lone pair stabilized by the solvent environment.

Validation of local p16 testing for determination of human papilloma virus status eligibility on a low risk oropharyngeal cancer trial - A Trans-Tasman Radiation Oncology Group study.

OBJECTIVE: Accurate determination of human papilloma virus (HPV) status is critical when identifying patients with oropharyngeal squamous cell carcinoma (OPSCC) who may be candidates for de-escalation trials. In this study we investigated whether local p16 screening, by immunohistochemistry (IHC), has high positive predictive value (PPV) for HPV status in a good prognosis HPV positive OPSCC (HPVOPSCC) population treated on a clinical trial. METHODS AND MATERIALS: Patients enrolled on the TROG 12.01 randomised trial for good prognosis HPVOPSCC were randomised based on local p16 IHC testing but subsequently had central p16 IHC and HPV RNA in situ hybridisation (HPV RNA ISH) testing. Correlations between the local and central p16 and central HPV RNA ISH were studied. The main outcome was the positive predictive value (PPV) of local pathology laboratory testing of p16. RESULTS: 176/182 patients had samples available for central testing. 172/176 were evaluable for central testing of p16, and all were confirmed to be p16 positive (172/172, 100%, 95% CI = [97.9%, 100%]). Similarly, 100% of those evaluable for HPV RNA ISH (155/155, 100%, 95% CI = [97.6%, 100%]) were confirmed HPV positive, indicating p16 overexpression driven by transcriptionally active HPV and a PPV of 100% for local p16 testing. CONCLUSIONS: Our results validate the suitability of local pathology laboratory p16 testing alone, in populations with a high attributable fraction of OPSCC due to HPV, to screen and enrol low risk HPVOPSCC patients onto de-intensification trials. This obviates the need for upfront more complex and expensive HPV assays and/or central laboratory testing.

Gastrointestinal Bleeding in a Pancreas Transplant Recipient: A Case to Remember.

BACKGROUND Pancreas transplantation has proven to be the most effective therapeutic option for insulin-dependent diabetes mellitus. However, despite advances in surgical technique and continuously improving outcomes, pancreas transplantation has the highest complication rate among all solid-organ transplants. Vascular complications in particular can be catastrophic, with graft- and life-threatening potential. Ectopic variceal bleeding is less common and is rarely reported in the literature. CASE REPORT A 51-year-old man presented with recurrent intermittent gastrointestinal bleeding (GIB) associated with hepatic dysfunction and portal hypertension 4 years after a successful pancreas-after-kidney transplant. Apart from positive serology for hepatitis E virus, all the other liver disease screening results were negative. He was extensively investigated with 6 computed tomography (CT) scans, 3 esophago-gastro-duodenoscopies (EGD), 3 colonoscopies, and 1 visceral arteriogram before the plausible diagnosis of ectopic trans-anastomotic variceal bleeding involving the pancreas transplant was established. Selective variceal catheterization and embolization were done with 3% sodium tetradecyl sulphate (STD). He remained free of bleeding after embolization. CONCLUSIONS This case report adds to the scanty literature on the management of ectopic variceal bleeding in a pancreas transplant recipient. Diagnosis of ectopic varix is usually challenging and frequently requires a visceral arteriogram. We describe a novel minimally-interventional technique to obtain source control and also discuss the complexity involved in the management, along with future implications.

Nucleophilic Thiols Reductively Cleave Ether Linkages in Lignin Model Polymers and Lignin.

Lignin may serve as a renewable feedstock for the production of chemicals and fuels if mild, scalable processes for its depolymerization can be devised. The use of small organic thiols represents a bioinspired strategy to cleave the ß-O-4 bond, the most common linkage in lignin. In the present study, synthetic ß-O-4 linked polymers were treated with organic thiols, yielding up to 90 % cleaved monomer products. Lignin extracted from poplar was also treated with organic thiols resulting in molecular weight reductions as high as 65 % (Mn ) in oxidized lignin. Thiol-based cleavage of other lignin linkages was also explored in small-molecule model systems to uncover additional potential pathways by which thiols might depolymerize lignin. The success of thiol-mediated cleavage on model dimers, polymers, and biomass-derived lignin illustrates the potential utility of small redox-active molecules to penetrate complex polymer matrices for depolymerization and subsequent valorization of lignin into fuels and chemicals.

Greener Routes to Biomass Waste Valorization: Lignin Transformation Through Electrocatalysis for Renewable Chemicals and Fuels Production.

Lignin valorization is essential for biorefineries to produce fuels and chemicals for a sustainable future. Today's biorefineries pursue profitable value propositions for cellulose and hemicellulose; however, lignin is typically used mainly for its thermal energy value. To enhance the profit potential for biorefineries, lignin valorization would be a necessary practice. Lignin valorization is greatly advantaged when biomass carbon is retained in the fuel and chemical products and when energy quality is enhanced by electrochemical upgrading. Though lignin upgrading and valorization are very desirable in principle, many barriers involved in lignin pretreatment, extraction, and depolymerization must be overcome to unlock its full potential. This Review addresses the electrochemical transformation of various lignins with the aim of gaining a better understanding of many of the barriers that currently exist in such technologies. These studies give insight into electrochemical lignin depolymerization and upgrading to value-added commodities with the end goal of achieving a global low-carbon circular economy.

Clinical and dosimetric risk stratification for patients at high-risk of feeding tube use during definitive IMRT for head and neck cancer.

INTRODUCTION: To identify organs to which dose limitation using intensity modulated radiotherapy (IMRT) can potentially modify the incidence and duration of feeding tube use, during and immediately following therapy for head and neck cancer. MATERIALS AND METHODS: One hundred and fourteen patients treated with definitive IMRT (± concurrent chemotherapy) head and neck mucosal cancers were included. Patients received a prophylactic feeding tube and followed up by a dietician for at least eight weeks post-radiotherapy. Salivary and swallowing organs were delineated for each patient. Tumour and dosimetric variables were recorded for all patients and analysed for incidence and duration of feeding tube use for at least 25% of dietary requirements. RESULTS: Multivariate analysis showed T-classification ≥3 and level II lymphadenopathy as independent significant predictors of incidence and duration of feeding tube use in oral cavity, pharyngeal and supraglottic primaries. Mean dose deposited in the cervical oesophagus over 36Gy further increased the incidence and duration of feeding tube use. Mean dose deposited in the base of tongue and superior pharyngeal constrictor muscles affected incidence and duration of feeding tube use, respectively. DISCUSSION: In patients treated with definitive IMRT, T-classification and Level II lymphadenopathy, combined with a mean cervical oesophagus dose over 36Gy can a stratify patients into eight distinct risk groups for using feeding tubes for at least 25% of their dietary requirements.

Quantitative Analysis of Infrared Spectra of Binary Alcohol + Cyclohexane Solutions with Quantum Chemical Calculations.

Hydrogen bonding has profound effects on the behavior of molecules. Fourier-transform infrared spectroscopy is the technique most commonly used to qualitatively identify hydrogen-bonding moieties present in a chemical sample. However, quantitative analysis of infrared (IR) spectra is nontrivial for the hydroxyl stretching region where hydrogen bonding is most prominently expressed in organic alcohols and water. Specifically, the breadth and extreme overlap of the O-H stretching bands, and the order of magnitude variability of their IR attenuation coefficients complicates the analysis. In the present work, sequential molecular dynamics simulations and quantum mechanical calculations are used to develop a function to relate the integrated IR attenuation coefficient to the vibrational frequencies of hydroxyl bands across the O-H stretching region. This relationship is then used as a guide to develop an attenuation coefficient scaling function to quantitatively determine concentrations of alcohols in a hydrocarbon solution from experimental IR spectra by integration across the entire hydroxyl frequency range.