Search

HPV-positive cancer is strongly immunogenic tumor which induces cell type response in surrounding microenvironment. Systemic inflammation is generally accompanied by cancer disease and it weakens cell response and negatively influences organism reaction to cancer The aim of present study was to compare laboratory parameters of the immune system: leukocyte count (WBC), neutrophil count (Neut) and lymphocyte count (Lym), monocyte count (Mono), C-reactive protein (CRP), Interleukine 6 (Il-6), in patients with HPV-positive and HPV-negative OPC. 75 patients were treated with curative intent with radiotherapy alone (32 %) or combined with platinum-based chemotherapy (68%). There were 47% patients with T1/2 and 53% with T3/4 of primary tumor stage and 44% and 56% of patients with N0 and N+ nodal stage disease, respectively. Complete blood counts (CBC), C-reactive protein (CRP) and Il-6 were estimated in blood or serum before and after the treatment. HPV DNA was determined in plasma by QPCR method. In patients with HPV-negative OPC WBC count (p=0,006 median: 6,88 vs 5,69), Lym count (p=0,02 median: 1,96 vs 1,49) and CRP (p=0,0001 median: 5,88 vs 1,35 mg/dl) was higher than for HPV-positive OPC before treatment. Additionally, in patients with HPV-negative OPC WBC count (p=0,03 median: 5,53 vs 4,17), Lym count (p=0,02 median: 0,69 vs 0,44), Mono count (p=0,003 median: 0,58 vs 0,43) and Il-6 (p=0,05 median: 25,53 vs 11,65 pg/ml) was higher than for HPV-positive OPC after therapy. Before treatment significantly longer overall survival (OS) for patients with low WBC count (p=0,001)(Fig.1), low concentration of CRP (p=0,0001) (Fig. 2) and Il-6 (p=0,01) was also found. Inflammation processes are more severe in HPV-negative OPC. Low levels of inflammatory indicators like WBC count, Lym count, CRP, Il-6 may be associated with longer OS in this group of patients. Systemic inflammation reflects host reaction on cancer, characterized by a significant weakness of cellular immunity. It is more characteristic for patients with HPV–negative OPC [ABSTRACT FROM AUTHOR]

Simple Summary: Patients treated with definitive accelerated radiotherapy (DART) struggle with low quality of life, pain and persistent treatment-related symptoms even many years after the treatment. Everyday pain in the head, neck and shoulder areas is present among almost all HNC survivors treated with DART. One-third of the examined DART patients were depressed. The depressed group scored significantly worse in most of the quality-of-life subscales and suffered more intense pain than the non-depressed. Head and neck cancer survivors, especially those who are depressed, may require additional psychosocial, physiotherapeutic and medical intervention programs. (1) Background: The goal of this study is to evaluate psychological tolerance and health-related quality of life (QOL) in head and neck (HN) cancer patients treated with definitive accelerated radiotherapy (DART). (2) Methods: 76 recurrence-free patients eligible for the study, who were treated with DART in the CAIR-2 phase III clinical study (median of follow-up = 47 months), completed EORTC QLQ-C30 with the H&N35 module, Hospital Anxiety and Depression Scale (HADS) and Visual–Analog Scales (VAS) of pain in HN and the neck/arm areas. (3) Results: The most dominant symptoms measured with QLQ-C30 were as follows: fatigue (44/100), sleeplessness (39/100), financial problems (38/100) and pain (32/100). Within the H&N35, the highest scores were reported on the subscales of sticky saliva (60/100), mouth dryness (65/100) and increased intake of painkillers (50/100). Pain (VAS) was reported by 87% (HN area) and 78% (shoulder area) of the patients, with a mean score of 3/10. One-third of the patients reported depressive moods (HADS ≥ 15 points) with an average score of 12.5/42 p. The depressed group, who smoked more as compared to the non-depressed group before DART (96% vs. 78%) and required steroids treatment (85% vs. 58%) during DART, also scored significantly worse on 23 of the 35 subscales of QLQ-C30 and H&N35 and experienced more intense pain (VAS). Women and less-advanced patients scored better in several aspects of quality of life. (4) Conclusions: Patients treated with DART struggle with low quality of life and persistent treatment-related symptoms including constant pain. HNC survivors, especially those who are depressed, may require additional psychosocial, rehabilitation and medical intervention programmes. [ABSTRACT FROM AUTHOR]

The paper aims to show the multilevel and complex cooperation and the inclusion of the psychotherapist leading the psychotherapy in the medical team at the radiotherapy and clinical oncology clinic. We illustrate these interventions with the case of Stan. This 43‐year‐old firefighter was diagnosed with advanced head and neck cancer and pre‐existing mental health problems meeting the criteria of ICD‐10: obsessive‐compulsive disorder, post‐traumatic stress disorder and psychoactive substance abuse. During the treatment, suicidal thoughts and impulses emerged, triggered at the hospital by electronic noises and the feeling of entrapment without a way out. This situation put the patient at high risk and the whole healthcare team needed an urgent effective response. The patient agreed to stay in the secured room, where he was cared for by doctors, nurses, a dietitian, and a psychotherapist. He actively attended daily sessions with noticeable engagement. Psychotherapy sessions focused on alleviating posttraumatic stress disorder and OCD. Mindfulness and breathwork‐based exercises were implemented to increase non‐judgemental self‐awareness and regulate the over‐aroused nervous system. As a result, the patient's mental health has improved and the completion of the cancer treatment was possible. Psychotherapy, good therapeutic alliance, and attentive teamwork effectively managed his mental health and treatment‐related symptoms. [ABSTRACT FROM AUTHOR]

Wegener's granulomatosis is a rare disease (10 per 1 000 000 new cases per year), etiologically connected with necrotizing vasculitis of small to medium-size vessels. The disease occurs predomi- nantly in the upper respiratory tract, lungs and kidneys, but any organmay be affected during the course of the illness. Itmay be difficult to diagnose, especially when c-ACNA antibodies (serologic symptom of Wegener's granulomatosis) are undetectable and chest X-ray is normal. Early diagnosis is crucial for treatment results. Untreated diseasemay lead to death. Cyclophosphamide used simultaneously with prednisone is the treatment of choice as the first line procedure. Resistance to standard systemic treatment may be a significant problem. New drugs (rituximab, infliximab) are still under clinical investigation, with promising results. Very limited data concerning effectiveness of radiation therapy exist. We present a report of a female patient with solitary form of Wegener's granulomatosis located in the facial region, who underwent successful radiation therapy with a complete response. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate severity of acute mucosal reactions (AMR) caused by conventional (CF) and accelerated fractionation (AF) regimens using a modified Dische system and to analyze differences in incidence and severity of AMR according to frequency and regularity of scoring. Methods and Materials: Sixty-six consecutive patients (33 CF, 33 AF) with head and neck cancer irradiated with 5 fractions in 5 days per week (CF) or with 7 fractions in 7 days (AF) to a total dose of 70 Gy. A modified Dische system was used for daily quantitation of AMR during radiotherapy until complete healing. Results: Confluent mucositis (CM) was noted in 79% of patients in the CF group and 85% in the AF group. In 24% of the CF group and 18% of the AF group the CM presented a wave-like pattern. In 55% of CF and 67% of AF a classic triphasic pattern was noted. In 12 patients acute reactions did not transgress the level of spotted mucositis. The present study clearly shows that quantitation of the incidence and severity of acute mucosal effects strongly depends on frequent and regular scoring. A significant difference in the incidence of CM between the CF and AF groups was noted, mainly in weeks 4–6 of irradiation. When once-weekly irregular instead of daily scoring was evaluated, the incidence of CM was underestimated by approximately 20–36%. Conclusions: Acute mucosal reactions occur as a complex of morphologic and functional disorders with individual intensity, even among patients treated with the same fractionation regimen. In some cases they present a “wave-like” pattern during irradiation. Therefore, precise quantitation of acute effects requires regular and frequent scoring. [Copyright &y& Elsevier]

Supported by the National Science Centre, Poland, 2020/39/O/NZ5/02625. Induction chemotherapy (iCH) although is not a standard approach, is often used in clinical practice for patients with advanced head and neck cancer (HNSCC). Tumor regression is a potential goal of induction treatment to reduce target volume in the second stage of treatment - radiochemotherapy or radiotherapy. In this study the most common iCH, TPF (docetaxel, cisplatin, and 5-fluoruracil) has been replaced with two-drugs regimen combined with low-dose radiation. Complementary mechanisms of action and excellent radiation sensitization of drugs together with hyperradiosensitivity (HRS) phenomenon of low-dose fractionated radiation therapy may be beneficial for patients with bulky disease. Additionally, lower toxicity could be expected for two-drugs modality. Preliminary results on effectiveness and toxicity has been presented. The group consisted of 27 patients treated due to advanced HNSCC in National Research Institute of Oncology, Gliwice branch between 2020 and 2023. There were 23 (85%) men and 4 (15%) women in the median age of 60 years. In most cases primary tumor site was oropharynx followed by hypopharynx and CUP in 17 (63%), 7 (26%) and 3 (11%) cases respectively. All patients presented advanced stage - III stage in 16 cases (59%) and IV stage in 11 cases (41%). HPV- positive tumors were found in 13 (48%) patients. There were 2 cycles of iCHT consisting of carboplatin (AUC 6) and paclitaxel (75 mg/m2) combined with low-dose radiotherapy 2 x 0.5 Gy on days 1, 8 and 15. Additionally, two doses of 0.5 Gy was given on day 2. CT, MRI and PET-CT scans were performed to estimate the staging of the cancer, all according to the 8th edition of the TNM classification for malignant tumors. The volume of the primary tumor and metastatic lymph nodes were estimated in cm3 before and after induction radiochemotherapy with low dose fractionation radiotherapy to analyze the potential value of tumor volume regression. After ICHRTL, all patients were qualified for the second stage of treatment - radiochemotherapy in 24 cases and radiotherapy in 3 cases, respectively. To investigate the presence of HRS effect, fibroblasts were irradiated in vitro with doses ranging from 0.1 to 4 Gy (6-MV X-ray beam) and cell radiosensitivity was estimated by flow cytometry-based clonogenic survival assay and RIANS test (pATM and H2AX foci assays). [Display omitted] Clinical and experimental data will be presented.The mean volumes of tumor and metastatic lymph nodes among 27 patients before ICHRTL were 32.5 cm3 (Vt) and 45.1 cm3 (Vn), respectively. After ICHRTL, these mean values were 17.2 cm3 (Vt) and 22.2 cm3 (Vn). Wilcoxon test analize showed significant decrease in T volume (Vt) and N volume (Vn) before and after iCHRTL (p=0.003) and p=0.00008) respectively. Due to complications 16 patients (60%) did not receive the full dose of chemotherapy and radiotherapy (ICHRTL). Leukopenia and neutropenia occurred in 12 (44%) and 11 (40%) patients respectively. Poor drug tolerance (vomiting, nausea, abdominal pain) was observed in 3 (11%) patients, and renal failure in 1 (4%) patient. Among normal skin fibroblasts assessed from 21 patients two demonstrated HRS effect. The use of ICHRTL in patients with advanced HNSCC is a low-toxicity and effective method. The obtained regression of tumor volume (Vt) and metastatic lymph nodes (Vn) in most patients managed to reduce the high dose area in the second stage of treatment (radiotherapy/radiochemotherapy). Further observations are needed to estimate the potential role of decrease in T volume (Vt) and N volume (Vn) after ICHRTL on the expected survival of patients. [ABSTRACT FROM AUTHOR]

Purpose: To report long-term results of randomized trial comparing 2 accelerated fractionations of definitive radiation therapy assessing the need to irradiate during weekend in patients with head and neck squamous cell carcinoma. Methods and Materials: A total of 345 patients with SCC of the oral cavity, larynx, and oro- or hypo-pharynx, stage T2-4N0-1M0, were randomized to receive continuous accelerated irradiation (CAIR: once per day, 7 days per week) or concomitant accelerated boost (CB: once per day, 3 days per week, and twice per day, 2 days per week). Total dose ranged from 66.6-72 Gy, dose per fraction was 1.8 Gy, number of fractions ranged from 37-40 fractions, and overall treatment time ranged from 37-40 days. Results: No differences for all trial end-points were noted. At 5 and 10 years, the actuarial rates of local-regional control were 63% and 60% for CAIR vs 65% and 60% for CB, and the corresponding overall survival were 40% and 25% vs 44% and 25%, respectively. Confluent mucositis was the main acute toxicity, with an incidence of 89% in CAIR and 86% in CB patients. The 5-year rate of grade 3-4 late radiation morbidity was 6% for both regimens. Conclusions: Results of this trial indicate that the effects of accelerated fractionation can be achieve by delivering twice-per-day irradiation on weekday(s). This trial has also confirmed that an accelerated, 6-weeks schedule is a reasonable option for patients with intermediate-stage head-and-neck squamous cell carcinoma because of the associated high cure rate and minimal severe late toxicity. [Copyright &y& Elsevier]

Background: Early detection of treatment failure may improve clinical outcome and overall survival in patients with head and neck cancer after first-line treatment. Circulating cell-free HPV16 DNA (cfHPV16 DNA) was evaluated as a possible complementary marker to radiological assessment of early response in patients with HPV-related oropharyngeal cancer (OPC) after radiotherapy alone or combined with chemotherapy.Methods: The study included 66 patients with HPV-related OPC receiving radical radiotherapy alone or in combination with chemotherapy. cfHPV16 DNA was assessed in the blood of all patients before treatment using TaqMan-based qPCR. Subsequent analysis of cfHPV16 DNA was performed 12 weeks after treatment completion, along with radiological assessment of early treatment results.Results: Complete (CRR) and incomplete radiological response (IRR) was found in 43 (65%) and 23 (35%) patients respectively. cfHPV16 DNA was present in 5 (28%) patients with IRR, while only in 1 (4%) with CRR. Three of five patients with IRR that were positive for cfHPV16 DNA exhibited histopathologically confirmed local or regional treatment failure, and other two developed distant metastases. None of the patients with negative cfHPV16 DNA presented disease failure.Conclusion: The post-treatment assessment of cfHPV16 DNA in patients with HPV-related OPC may be used as a complementary biomarker to conventional imaging-based examinations for early identification of treatment failure. [ABSTRACT FROM AUTHOR]

Between January 2017 and July 2018 103 patients were included in a prospective study of erythropoietin (EPO) monitoring. The group consisted of 33% patients with oropharynx, 29% with oral cavity, 13% with nasopharynx, 6% with larynx, 6% with hypopharynx, 8% with unknown primary cancer, 4% with nasal cavity, and 1% with salivary gland cancer. Clinic stage: T4 - 50, T3 - 21, T2 - 14, T1 -10, T0 - 8, and N3 - 19, N2 - 61, N1 -10, N0 - 13. All patients received from one to four cycles of induction chemotherapy. EPO was measured in blood serum by enzyme-labelled chemiluminescent immunometric assay, using an Immulite 2000XPi analyser before the administration and on day 11 of each chemotherapy cycle. During induction chemotherapy the EPO level was elevated in all patients, which is expressed by means of medians: 10.7 (p = 0.000001) in the middle of cycle 1; 10.9 (p = 0.66) before cycle 2; 14.35 (p = 0.000177) in the middle of cycle 2; 14.95 (p = 0.39) before cycle 3, 17.00 (p = 0.00078) in the middle of cycle 3, and 20.9 after cycle 3 (p = 0.41). The correlation analysis conducted indicates that the administration of one chemotherapy dose results in higher EPO release (two-fold increase in EPO concentration) which intensifies reticulocytes (REC) production but without haemoglobin concentration in reticulocytes (HGB-REC) growth. In consequence, it leads to a decrease in RBC and HGB concentration (29-32 cases). The administration of two and three chemotherapy doses results in the subsequent higher release of EPO, which does not intensify REC production. In consequence, anaemia increases (35 cases). [ABSTRACT FROM AUTHOR]

Paragangliomas of the head and neck are a group of neoplasms which occur very rarely. Most of them are benign tumours. Tinnitus, headaches and dysfunction of the cranial nerves are typical symptoms. Some paragangliomas have metastatic abilities and they can produce catecholamines. There are some typical imaging features in CT and MRI scans which help to determine the correct diagnosis without the necessity of performing a biopsy which can be associated with a haemorrhage risk. Therapeutic management consists of the choice between an active observation, surgical procedure, as well as radiotherapy and systemic therapy in the case of malignant paragangliomas. [ABSTRACT FROM AUTHOR]

Background Recent studies have indicated that human papillomavirus is an etiologic agent for a subset of head and neck cancers associated with better prognosis, therefore, prompt confirmation of such etiology seems to be crucial for choosing the optimal therapeutic option. Standard HPV diagnosis is currently based on histopathological material. In the present study, the novel diagnostic method based on pharyngeal brush biopsy is proposed. Objectives The aim of this study was to evaluate the usefulness of the Real-Time PCR-based (RT-PCR) test in detecting HPV-related cancer of the oropharynx using superficial scraps taken from the oropharyngeal region. Study design Ninety patients with head and neck squamous cell cancer were enrolled in the study. The presence of HPV DNA in pharyngeal superficial scrapes assessed by RT-PCR was compared to the HPV status in the tumor tissue samples determined by a combined RT-PCR/P16 INK4A expression algorithm. Analytical sensitivity and specificity were calculated and the clinical outcome was analyzed in correlation to the HPV status. Results HR-HPV DNA in pharyngeal swabs was revealed in 25 cases (28.4%) and simultaneously confirmed in all corresponding tissue samples. Sensitivity and specificity of the viral status assessment in the brush biopsies in respect to the RT-PCR/P16 INK4A 20 were 100% and 96.2%, respectively. HR-HPV positive status was associated with an excellent clinical outcome and reduced hazard ratio of recurrence and disease-related death. Conclusions The proposed novel method of HPV status assessment using RT-PCR and superficial scraps appeared to be highly sensitive, specific, and useful in predicting the clinical outcome. [ABSTRACT FROM AUTHOR]

The retrospective chart review of 110 patients with T2 supraglottic cancer who underwent radiotherapy was performed to correlate tumor volume with other prognostic factors and to analyze its impact on treatment results. Patients with involved nodes, poor histopathological tumor differentiation, or hemoglobin concentration ≤ 14.3 g/dl had significantly larger tumors. Patients with large tumors had significantly lower 5-year local control rate, overall survival rate and presented significantly higher risk of nodal involvement and the ratio of poor histopathological differentiation of the tumor. Tumor volume significantly impacts radiotherapy outcome and should be considered to optimize treatment strategy for patients with T2 supraglottic cancer. [ABSTRACT FROM AUTHOR]

Background Conformal intensity-modulated radiation therapy (IMRT) involves irradiation of large volume of normal tissue with low and medium doses, biological relevance of which is not clear yet. Serum proteome features were used here to study the dose-volume effects in patients irradiated with IMRT due to head and neck cancer. Methods Blood samples were collected before and during RT, and also about one month and one year after the end of RT in a group of 72 patients who received definitive treatment. Serum proteome profiles were analyzed using MALDI-ToF mass spectrometry in 800-14,000 Da range. Results Major changes in serum proteome profiles were observed between pre-treatment samples and samples collected one month after RT. Radiation-related changes in serum proteome features were affected by low-to-medium doses delivered to a large fraction of body mass. Proteome changes were associated with intensity of acute radiation toxicity, indicating collectively that RT-related features of serum proteome reflected general response of patient's organism to irradiation. However, short-term dose-related changes in serum proteome features were not associated significantly with the long-term efficacy of the treatment. Conclusions The effects of low and medium doses of radiation have been documented at the level of serum proteome, which is a reflection of the patient's whole body response. [ABSTRACT FROM AUTHOR]

Purpose: The plasma proteome was analysed as a potential source of markers of radiosensitivity in patients treated with definitive radiotherapy for head and neck cancer. Materials and methods: Acute mucosal reactions that developed during radiotherapy were assessed in 55 patients. Blood samples were collected from each patient before the treatment and also from 50 healthy donors. The low-molecular-weight fraction of the plasma proteome (2,000--10,000 Da range) was analysed by the Matrix-Assisted Laser Desorption Ionisation mass spectrometry. The capacity for DNA break repair was assessed by the comet assay using lymphocytes irradiated in  vitro. Results: Spectral components registered in plasma samples were used to build classifiers that discriminated patients from healthy individuals with about 90%% specificity and sensitivity (components of 4469, 6929 and 8937 Da were the most essential for cancer classification). Four spectral components were identified (2219, 2454, 3431 and 5308 Da) whose abundances correlated with a maximal intensity of the acute reaction. Several spectral components whose abundances correlated with the rate of DNA repair in irradiated lymphocytes were also detected. Additionally, a more rapid escalation of an acute reaction was correlated with a higher level of unrepaired damage assessed by the comet assay. Conclusions: The plasma proteome could be considered as a potential source of predictive markers of acute reaction in patients with head and neck cancer treated with radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To update 5-year results of a previously published study on special 7-days-a-week fractionation continuous accelerated irradiation (CAIR) for head-and-neck cancer patients. Methods and Materials: One hundred patients with squamous cell carcinoma of head and neck in Stage T2-4N0-1M0 were randomized between two definitive radiation treatments: accelerated fractionation 7 days a week including weekends (CAIR) and conventional 5 days a week (control). Hence the overall treatment time was 2 weeks shorter in CAIR. Results: Five-year local tumor control was 75% in the CAIR group and 33% in the control arm (p < 0.00004). Tumor-cure benefit corresponded with significant improvement in disease-free survival and overall survival rates. Confluent mucositis was the main acute toxicity, with the incidence significantly higher in CAIR patients than in control (respectively, 94% vs. 53%). When 2.0-Gy fractions were used, radiation necrosis developed in 5 patients (22%) in the CAIR group as a consequential late effect (CLE), but when fraction size was reduced to 1.8 Gy no more CLE occurred. Actuarial 5-year morbidity-free survival rate was similar for both treatments. Conclusions: Selected head-and-neck cancer patients could be treated very effectively with 7-days-a-week radiation schedule with no compromise of total dose and with slight 10% reduction of fraction dose (2 Gy–1.8 Gy), which article gives 1 week reduction of overall treatment time compared with standard 70 Gy in 35 fractions over 47–49 days. Although this report is based on the relatively small group of patients, its results have encouraged us to use CAIR fractionation in a standard radiation treatment for moderately advanced head-and-neck cancer patients. [Copyright &y& Elsevier]

Purpose/Objective: Our goal was to analyze the repopulation of surviving tumor cells during a treatment gap in radiotherapy for head-and-neck cancer.Methods and Materials: Clinical material is based on the records of 1502 patients treated by radiotherapy alone in Maria Sklodowska-Curie Memorial Institute in Gliwice during the period between1980 and 1989. All patients had histologically confirmed squamous cell carcinoma of the larynx or pharynx. The mean gap duration was 9 days. Only 10% of patients were treated without gaps. The dose per fraction was in the range of 1.5 to 2.5 Gy. Patient data were fitted directly to the mixed linear-quadratic model using maximum-likelihood estimation. Tumor stage or tumor localization was introduced into the equation as a categorical variable. Tumor proliferation was estimated by dividing the treatment gaps into three groups: the first 2 weeks, second 2 weeks, and the period after 4 weeks of irradiation.Results: Tumor control probability was significantly correlated with radiation dose, tumor progression (according to TNM), overall treatment time, and gap duration. Laryngeal cancers had a better prognosis than cancers of the oro- and nasopharynx. Significant tumor repopulation was found after the first 2 weeks of radiotherapy. During the treatment gap, the proliferation rate was equal to 0.75 Gy/day. During the days with irradiation, repopulation was slower and equal to 0.2 Gy/day.Conclusion: The repopulation of tumor cells is faster during a gap than during the normal days of irradiation. Accelerated repopulation probably starts soon after 2 weeks of irradiation. [Copyright &y& Elsevier]

Background: Conformal intensity-modulated radiation therapy (IMRT) involves irradiation of large volume of normal tissue with low and medium doses, biological relevance of which is not clear yet. Serum proteome features were used here to study the dose-volume effects in patients irradiated with IMRT due to head and neck cancer.Methods: Blood samples were collected before and during RT, and also about one month and one year after the end of RT in a group of 72 patients who received definitive treatment. Serum proteome profiles were analyzed using MALDI-ToF mass spectrometry in 800-14,000 Da range.Results: Major changes in serum proteome profiles were observed between pre-treatment samples and samples collected one month after RT. Radiation-related changes in serum proteome features were affected by low-to-medium doses delivered to a large fraction of body mass. Proteome changes were associated with intensity of acute radiation toxicity, indicating collectively that RT-related features of serum proteome reflected general response of patient's organism to irradiation. However, short-term dose-related changes in serum proteome features were not associated significantly with the long-term efficacy of the treatment.Conclusions: The effects of low and medium doses of radiation have been documented at the level of serum proteome, which is a reflection of the patient's whole body response. [ABSTRACT FROM AUTHOR]