Impact of deep learning-determined smoking status on mortality of cancer patients: never too late to quit.

BACKGROUND: Persistent smoking after cancer diagnosis is associated with increased overall mortality (OM) and cancer mortality (CM). According to the 2020 Surgeon General's report, smoking cessation may reduce CM but supporting evidence is not wide. Use of deep learning-based modeling that enables universal natural language processing of medical narratives to acquire population-based real-life smoking data may help overcome the challenge. We assessed the effect of smoking status and within-1-year smoking cessation on CM by an in-house adapted freely available language processing algorithm. MATERIALS AND METHODS: This cross-sectional real-world study included 29 823 patients diagnosed with cancer in 2009-2018 in Southwest Finland. The medical narrative, International Classification of Diseases-10th edition codes, histology, cancer treatment records, and death certificates were combined. Over 162 000 sentences describing tobacco smoking behavior were analyzed with ULMFiT and BERT algorithms. RESULTS: The language model classified the smoking status of 23 031 patients. Recent quitters had reduced CM [hazard ratio (HR) 0.80 (0.74-0.87)] and OM [HR 0.78 (0.72-0.84)] compared to persistent smokers. Compared to never smokers, persistent smokers had increased CM in head and neck, gastro-esophageal, pancreatic, lung, prostate, and breast cancer and Hodgkin's lymphoma, irrespective of age, comorbidities, performance status, or presence of metastatic disease. Increased CM was also observed in smokers with colorectal cancer, men with melanoma or bladder cancer, and lymphoid and myeloid leukemia, but no longer independently of the abovementioned covariates. Specificity and sensitivity were 96%/96%, 98%/68%, and 88%/99% for never, former, and current smokers, respectively, being essentially the same with both models. CONCLUSIONS: Deep learning can be used to classify large amounts of smoking data from the medical narrative with good accuracy. The results highlight the detrimental effects of persistent smoking in oncologic patients and emphasize that smoking cessation should always be an essential element of patient counseling.

Intravenous but not intrathecal central nervous system-directed chemotherapy improves survival in patients with testicular diffuse large B-cell lymphoma.

BACKGROUND: Testicular lymphoma is a rare malignancy affecting mainly elderly men, the majority representing diffuse large B-cell lymphoma (DLBCL). Its relapse rate is higher than that of nodal DLBCL, often affecting the central nervous system (CNS) with dismal prognosis. PATIENTS AND METHODS: We searched for patients with testicular DLBCL (T-DLBCL) involvement from the pathology databases of Southern Finland University Hospitals and the Danish Lymphoma Registry. Clinical information was collected, and outcomes between treatment modalities were evaluated. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. RESULTS: We identified 235 patients; of whom, 192 were treated with curative anthracycline-based chemotherapy. Full survival data were available for 189 patients. In univariate analysis, intravenous CNS-directed chemotherapy, and irradiation or orchiectomy of the contralateral testis translated into favourable PFS, DSS and OS, particularly among the elderly patients (each p ≤ 0.023). Intrathecal chemotherapy had no impact outcome. In multivariate analyses, the advantage of intravenous CNS-directed chemotherapy (hazard ration [HR] for OS, 0.419; 95% confidence interval [CI], 0.256-0.686; p = 0.001) and prophylactic treatment of contralateral testis (HR for OS, 0.514; 95% CI, 0.338-0.782; p = 0.002) was maintained. Rituximab improved survival only among high-risk patients (International Prognostic Index≥3, p = 0.019). The cumulative risk of CNS progression was 8.4% and did not differ between treatment modalities. CONCLUSION: The results support the use of CNS-directed chemotherapy and prophylactic treatment of the contralateral testis in patients with T-DLBCL involvement. Survival benefit appears resulting from better control of systemic disease rather than prevention of CNS progression.

Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study.

BACKGROUND: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. RESULTS: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. CONCLUSIONS: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov. identifier NCT01502982.

Very high quantitative tumor HER2 content and outcome in early breast cancer.

BACKGROUND: It is unknown how a very high tumor total HER2 (human epidermal growth factor receptor-2) content (H2T) influences outcome in early breast cancer treated with adjuvant trastuzumab plus chemotherapy. PATIENTS AND METHODS: H2T was measured using a novel quantitative assay (HERmark(®)) from formalin-fixed tumor tissue of 899 women who participated in the FinHer trial (ISRCTN76560285). In a chromogenic in situ hybridization (CISH) test, 197 (21.9%) patients had HER2-positive cancer and were randomly assigned to receive trastuzumab or control. RESULTS: Cancer H2T levels varied 1808-fold. High H2T levels were correlated with a positive HER2 status by CISH (P < 0.0001). A nonlinear association was present between H2T and the hazard of distant recurrence in a subpopulation treatment effect pattern plot analysis in CISH-positive disease. Patients with very high H2T (defined by ≥22-fold the median of HER2-negative cancers; 13% of CISH-positive cancers) did not benefit from adjuvant trastuzumab [hazard ratio (HR) 1.23; 95% confidence interval (CI) 0.33-4.62; P = 0.75], whereas the rest of the patients with HER2-positive disease by CISH (87%) did benefit (HR 0.52; 95% CI 0.28-1.00; P = 0.050). CONCLUSION: Patients with HER2-positive breast cancer with very high tumor HER2 content may benefit less from adjuvant trastuzumab compared with those whose cancer has more moderate HER2 content.

Biodistribution of [11C] methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo.

[N-methyl-11C]alpha-Methylaminoisobutyric acid (11C-MeAIB) is a potentially useful tracer for positron emission tomography (PET) studies on hormonally regulated system A amino acid transport. 11C-MeAIB is a metabolically stable amino acid analogue specific for system A amino acid transport. We evaluated the biodistribution of 11C-MeAIB in rats and humans to estimate the usefulness of the tracer for in vivo human PET studies, for example, on regulation of system A amino acid transport and on tumour imaging. Healthy Sprague-Dawley rats (n=14) were killed 5, 20, 40 or 60 min after the injection of 11C-MeAIB, and the tissue samples were weighed and counted for 11C radioactivity. Ten lymphoma patients with relatively limited tumour burden underwent whole-body (WB) PET imaging with 11C-MeAIB. In addition, three other patients had dynamic PET scanning of the head and neck area, and the tracer uptake was quantitated by calculating the kinetic influx constants (Ki values) for the tracer. In animal studies, the highest activity was detected in the kidney, pancreas, adrenal gland and intestines. In humans, the highest activity was found in the salivary glands, and after that in the kidney and pancreas, similar to the results in animal studies. Rapid uptake was also detected in the skeletal muscle. In the graphical analysis, linear plots were obtained, and the mean fractional tracer uptake values (Ki) of the parotid glands (n=3) and cervical muscles (n=3) were 0.039+/-0.008 min(-1) and 0.013+/-0.006 min(-1), respectively. The Ki value of the tumour (n=1) was 0.064 min(-1). Higher uptake of 11C-MeAIB into the tumour tissue was encountered. These results encourage further 11C-MeAIB PET studies in humans on the physiology and pathology of system A amino acid transport and on tumour detection.

Experience in qualitative and quantitative FDG PET in follow-up of patients with suspected recurrence from head and neck cancer.

We evaluated positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) in the detection of recurrent head and neck cancer, and compared visual and quantitative interpretation of PET images for their accuracy in the identification of tumour recurrence. Sixty-two FDG PET studies were performed in 56 patients having a total of 81 lesions, which were clinically suspected for recurrent carcinoma of the head and neck. The PET images were interpreted visually, and tracer uptake was quantitated as the standardised uptake value adjusted to body weight (SUV). Sensitivity of visual interpretation of the PET images for the presence of malignancy ranged from 84 to 95%, and specificity from 84 to 93%, respectively, depending on the selected scheme for grading of the lesions. Malignant lesions accumulated significantly more FDG than the benign ones (the median SUVs were 6.8 and 3.3, respectively, P<0.001). However, there was a wide overlap of the FDG uptake values between these two groups. Hence, the highest accuracy of quantitative analysis in correct identification of tumour recurrence (75% at Receiver Operating Curve analysis) was inferior to that of visual analysis (89%). FDG PET is feasible for the detection of recurrent head and neck cancer. Although quantitation of FDG uptake using SUV shows significantly higher tracer concentrations for malignant than benign lesions, the wide overlap of individual SUVs between these two groups is a serious concern in diagnostic evaluation. Therefore, in clinical practice it may be preferable to identify the presence of tumour recurrence within this patient group by qualitative interpretation of the PET images.

Nodal staging of lymphoma with whole-body PET: comparison of.

UNLABELLED: Accurate staging is elementary for optimal management of malignant lymphoma. Advanced cases may be curable with multidrug chemotherapy combined with radiotherapy, whereas limited disease can sometimes be cured by local radiotherapy only. Recently, FDG imaging with whole-body PET (WB PET) has been introduced as an accurate method for staging lymphoma. We evaluated the usefulness of L-[methyl-11C]methionine (MET) in comparison with FDG as a tracer for nodal staging of lymphoma with WB PET. METHODS: Nineteen patients with untreated, histologically proven malignant lymphoma underwent WB PET imaging with MET and FDG within 1 wk before treatment. Fourteen patients had non-Hodgkin's lymphoma (NHL), and 5 had Hodgkin's disease (HD). Two of these 19 patients were excluded from the final analysis because of hyperglycemia. WB PET images using FDG and MET were visually compared by 3 independent interpreters, and the PET findings were correlated with the data on the basis of conventional staging studies. RESULTS: Fifty-five of 178 lymph node regions were classified as diseased both by FDG PET and by CT, and 54 of 178 were classified as diseased both by MET PET and by CT. In addition, 11 lymph node regions that CT showed to be normal avidly accumulated FDG. Ten of these lymph node regions also had clear uptake of MET. Another 4 and 5 lymph node regions were enlarged at CT but were judged to be normal by FDG and MET PET, respectively. In nodal staging, both FDG PET and MET PET would have upstaged the disease in 3 patients. MET PET would also have downstaged the disease in 1 patient. CONCLUSION: FDG and MET seem to be comparable in the detection of lymphoma by WB PET. However, visual interpretation of the images tends to be hampered more by physiologic accumulations of MET than by normal accumulations of FDG, and MET may be preferable to FDG in hyperglycemic patients undergoing staging studies with PET.

Evaluation of early response to radiotherapy in head and neck cancer measured with [11C]methionine-positron emission tomography.

PURPOSE: To evaluate whether positron emission tomography (PET) with carbon-11-methionine (MET) can be used for detection of early response to external beam radiotherapy (RT) in untreated head and neck cancer using locoregional control and survival as study endpoints. MATERIALS: Fifteen patients with head and neck cancer underwent a MET PET study before RT and after a median dose of 24 Gy. Fractionation was standard (n = 6) or hyperfractionated (n = 9), and 13 out of 15 patients had planned surgery after RT. SUV was calculated for primary tumor (n = 13) or largest lymph node metastasis in two patients of whom one had his primary excised before study enrollment and one presented with unknown primary tumor syndrome. METHODS: Attenuation corrected PET scans acquired 20-40 min from tracer injection were used for evaluation of MET uptake in tumors. A quantitative MET uptake index was expressed as standardized uptake value (SUV) or SUV(lean) (corrected for lean body mass). The PET results were correlated with clinical follow-up data. The median follow-up time is currently 28 months (range 22-34). RESULTS: A total of 13 primary tumors and 12 metastatic lymph nodes were visually identified in MET PET. In the first PET study the median SUV in tumor was 8.6 (range, 5.5-14.0). In the second PET study performed during RT the median SUV decreased to 5.7 (range, 3.1-8.2, P = 0.001). Two out of 15 patients showed no radiation-induced decrease in SUV. The median tumor SUV ratio of patients remaining in local control (CR) after RT was 0.7 (range 0.6-0.8, n = 6), and that of relapsing patients similarly 0.7 (range 0.5-1.0, n = 9, NS). The SUV ratio was not associated with survival time. The MET uptake of submandibular salivary glands decreased in all patients during the first two or three weeks of RT (P = 0.03). CONCLUSIONS: MET uptake in tumor shows a significant decrease during the first two to three weeks of RT of head and neck cancer. It appears that the rate of decrease in tracer uptake is comparable in relapsing patients and those who remain locally controlled and thus the use of MET PET for prediction of response to RT is limited.

[PET-findings in head-and neck cancers]. / PET-fynd vid huvud-och halscancer.

Head and neck cancer is very suitable for investigation with PET (positron emission tomography), usually owing to the locoregional spread at the time of diagnosis. Thus, the data collected enable any lesions present to be visualised. Evaluation of tumour metabolism with PET may simplify the diagnosis of metastases, and be of predictive value, enabling response to radiotherapy and cytostatic therapy to be predicted. It serves as a complement to CT (computed tomography) and MRI (magnetic resonance imaging) in the diagnosis of recurrence, and is thus useful in planning surgical intervention. Methods capable of distinguishing hypoxic or rapidly dividing cells can be useful in the choice of effective treatment methods such as hyperfractionated radiotherapy, drugs which enhance radiosensitivity, the degree of radical surgery, and the use of gene therapy.