A rare seizure: Tumor lysis syndrome after radiation therapy of a solid tumor.

Tumor lysis syndrome (TLS) is an uncommon but life threatening condition seen in oncology patients. Due to its underlying pathophysiology, it is classically associated with hematologic malignancies following chemotherapeutic treatment. In this article, we present a case of TLS in the setting of two rare features: a solid tumor malignancy and the absence of recent chemotherapy. We briefly review risk factors and the diagnosis of this potentially fatal but treatable condition.

[Endobronchic palliative brachytherapy]. / Brachythérapie endobronchique palliative.

Brachytherapy, the placement of an encapsuled radioactive source (Iridium) in or near a tumor, is a palliative therapeutic modality available for patients suffering of a bronchogenic cancer, especially if they present invalidating symptoms such an incoercible cough, haemoptysis, dyspnea. The treatment modality is indicated if chemotherapy or external irradiation are not possible. It is typically a team work.

X-irradiation of human bronchial cancer cells causes the bystander effects in normal bronchial cells in vitro.

Using X radiation commonly used in radiotherapy of cancers we investigated bystander interactions between human cells: irradiated A549 bronchial carcinoma human cells and non irradiated BEAS-2B normal bronchial epithelial cells. Non irradiated cells were incubated in medium transferred from irradiated A549 cells (ICM-irradiation conditioned medium) for 48h and next the chromosomal damage and apoptosis were estimated. Conditioned medium collected from irradiated cancer cells induced in non irradiated cells of the same line as well as in BEAS-2B normal cells genetic changes such as micronuclei, chromatid and chromosomal breaks and condensation of chromatin characteristic for processes of apoptosis. Addition of only 1% of conditioned medium to fresh medium was sufficient to induction of bystander response to normal bronchial cells. The presented results in this study could have implications for human radiation risk and in evaluating the secondary effects of radiotherapy.

[Clinical treatment outcome of grade III, non-small cell bronchogenic carcinoma using "whole-body" gamma-knife system].

The results of treatment of 80 patients with non-small cell lung cancer using the Chinese-made "Whole-Body" gamma-knife system were analyzed. Primary focus and involved lymph nodes were exposed. Neither gap between primary focus and involved lymph node or nodes, nor organs of the mediastinum were exposed. Exposure regimens were: STD = 4 Gy (2.5 - 10 Gy) 5 times a week; TTD=48 Gy (27-52 Gy) per primary focus and 4 Gy (3-6 Gy) 5 times a week; TTD = 43.5 Gy (30-52 Gy) per lymph nodes (105.6 - 150 Gy = equ.). Complete response was observed in 27.5% (22/80), partial - 42.5% (34/80). Overall survival was 61.3% among those sick for one year; 41.5%--2 years and 20.75%--3 years (mean survival time--20 months).

Multi-objective ensemble deep learning using electronic health records to predict outcomes after lung cancer radiotherapy.

Accurately predicting treatment outcome is crucial for creating personalized treatment plans and follow-up schedules. Electronic health records (EHRs) contain valuable patient-specific information that can be leveraged to improve outcome prediction. We propose a reliable multi-objective ensemble deep learning (MoEDL) method that uses features extracted from EHRs to predict high risk of treatment failure after radiotherapy in patients with lung cancer. The dataset used in this study contains EHRs of 814 patients who had not achieved disease-free status and 193 patients who were disease-free with at least one year follow-up time after lung cancer radiation therapy. The proposed MoEDL consists of three phases: (1) training with dynamic ensemble deep learning; (2) model selection with adaptive multi-objective optimization; and (3) testing with evidential reasoning (ER) fusion. Specifically, in the training phase, we employ deep perceptron networks as base learners to handle various issues with EHR data. The architecture and key hyper-parameters of each base learner are dynamically adjusted to increase the diversity of learners while reducing the time spent tuning hyper-parameters. Furthermore, we integrate the snapshot ensembles (SE) restarting strategy, multi-objective optimization, and ER fusion to improve the prediction robustness and accuracy of individual networks. The SE restarting strategy can yield multiple candidate models at no additional training cost in the training stage. The multi-objective model simultaneously considers sensitivity, specificity, and AUC as objective functions, overcoming the limitations of single-objective-based model selection. For the testing stage, we utilized an analytic ER rule to fuse the output scores from each optimal model to obtain reliable and robust predictive results. Our experimental results demonstrate that MoEDL can perform better than other conventional methods.

Complete remission after hypofractionated radiotherapy for a patient with inoperable adenoid cystic carcinoma of bronchus: A case report.

RATIONALE: Tracheobronchial adenoid cystic carcinoma (TACC) is a rare malignancy. Surgical resection remains the standard treatment of choice. But it is frequently unresectable due to its local extension. The practicability and safety of hypofractionated radiotherapy (HRT) for TACC remains unknown since most of the TACCs are centrally located. PATIENT CONCERNS: A 57-year-old female presented with paroxysmal cough, expectoration, and hemoptysis. DIAGNOSES: Computed tomography (CT) scan of the chest revealed a nodule originating from the wall of right primary bronchus, with 1.9*1.2 cm in size. Bronchoscope confirmed the node on the medial wall of the right primary bronchus extending towards the carina, with a close distance of 0.5 cm. Biopsy from the node was considered as adenoid cystic carcinoma (ACC). The clinical stage of the patient was T3N0M0. INTERVENTIONS: The patient underwent HRT with a total dose of 60Gy in twelve fractions. OUTCOMES: The patient experienced complete remission after HRT. No symptomatic radiation-induced toxicity (≥grade 2) was observed during the follow-up. LESSONS: HRT may be a safe and effective modality for inoperable TACC.

[Brachytherapy in the treatment of lung and tracheal cancer: current indications, methods, results]. / Brachyterapia raka pluca i tchawicy--wskazania, metody, wyniki leczenia.

Lack of improvement in treatment results of lung cancer leads to searching for new methods. One of the most distressing symptoms for lung cancer patients is airway obstruction due to the tumor, commonly resulting in dyspnea, postobstructive pneumonia, cough, or hemoptysis. Removal of endobronchial obstruction leads to quick improvement of clinical status and Quality of Life. Brachytherapy HDR of tracheal and lung cancer is a well-established method for the local treatment of patients with inoperable tumors of the tracheobronchial system. It seems that another promising treatment method of lung cancer is interstitial brachytherapy using permanent implants. The paper presents principles of brachytherapy, indications for this treatment and treatment results of tracheal and lung cancer. Indications for radical, palliative and interstitial treatment are discussed, respectively. Selected results of brachytherapy as an independent treatment and that combined with teletherapy, radical and, palliative are presented separately. Most commonly recognized complications are discussed which include: fatal pulmonary hemorrhage and fistula formation.

Whole-body hybrid imaging concept for the integration of PET/MR into radiation therapy treatment planning.

Modern radiation therapy (RT) treatment planning is based on multimodality imaging. With the recent availability of whole-body PET/MR hybrid imaging new opportunities arise to improve target volume delineation in RT treatment planning. This, however, requires dedicated RT equipment for reproducible patient positioning on the PET/MR system, which has to be compatible with MR and PET imaging. A prototype flat RT table overlay, radiofrequency (RF) coil holders for head imaging, and RF body bridges for body imaging were developed and tested towards PET/MR system integration. Attenuation correction (AC) of all individual RT components was performed by generating 3D CT-based template models. A custom-built program for µ-map generation assembles all AC templates depending on the presence and position of each RT component. All RT devices were evaluated in phantom experiments with regards to MR and PET imaging compatibility, attenuation correction, PET quantification, and position accuracy. The entire RT setup was then evaluated in a first PET/MR patient study on five patients at different body regions. All tested devices are PET/MR compatible and do not produce visible artifacts or disturb image quality. The RT components showed a repositioning accuracy of better than 2 mm. Photon attenuation of -11.8% in the top part of the phantom was observable, which was reduced to -1.7% with AC using the µ-map generator. Active lesions of 3 subjects were evaluated in terms of SUVmean and an underestimation of -10.0% and -2.4% was calculated without and with AC of the RF body bridges, respectively. The new dedicated RT equipment for hybrid PET/MR imaging enables acquisitions in all body regions. It is compatible with PET/MR imaging and all hardware components can be corrected in hardware AC by using the suggested µ-map generator. These developments provide the technical and methodological basis for integration of PET/MR hybrid imaging into RT planning.

Lack of apparent difference in outcome between clinically staged IIIA and IIIB non-small-cell lung cancer treated with radiation therapy.

The current American Joint Committee on Cancer (AJCC) staging system for bronchogenic carcinoma, which divides stage III M0 cases into stages IIIA and IIIB, is based on the observation that selected patients with IIIA disease (T3 or N2) can undergo complete surgical resection, in distinction to IIIB patients (T4 or N3). To understand the value of this system when applied to clinically staged (CS) patients treated with a standard nonoperative approach, the records of patients with squamous cell, large-cell, and adenocarcinoma of the lung treated with radiation therapy (RT) at the Fox Chase Cancer Center from 1978 to 1987 were reviewed. Three hundred sixteen patients were identified as having CS III M0 disease treated with single daily fraction RT without chemotherapy or sensitizers. Of these, the distinction between IIIA (166) and IIIB (140) could be made for 306 patients. The median survival time (MST) for all CS III patients was 9.6 months, and the 2-year survival was 17%. No difference was observed in MST between CS IIIA and IIIB patients (9.4 v 9.8 months, P = .78), in 2-year survival (17% v 18%), or in rate of first failure within the RT field (43% v 44%). MSTs for the 157 CS IIIA and IIIB patients with less than 5% weight loss and Zubrod performance status (PS) 0 to 1 were 13.0 and 15.8 months (P = .29), respectively. This lack of difference in outcome for CS IIIA and IIIB patients receiving RT has important implications in the design and stratification of future nonoperative trials for stage III lung cancer.

[Apropos of 5 cases of optic nerve tumors diagnosed during a 6-year-period]. / À propos de 5 cas de tumeurs du nerf optique sur une période de 6ans.

INTRODUCTION: Optic nerve tumors are uncommon and rarely described. By way of five patients treated at the University Hospital of Clermont-Ferrand, France, over a six-year-period, we discuss their clinical and radiological characteristics, their treatment and their course. OBSERVATIONS: We report two cases of optic nerve glioma in small children, two cases of optic nerve sheath meningioma and a 57-year-old patient treated for lung cancer with an optic nerve metastasis and choroidal and brain metastases. The diagnosis was confirmed by imaging in all patients and histologically for the cases of optic nerve glioma. RESULTS: The children with glioma were exclusively treated with chemotherapy, the two women with meningioma exclusively with radiation therapy, and the man with the optic nerve metastasis by chemotherapy and radiotherapy. The tumors were stabilized in all cases except for a progression in one case of glioma, one year after treatment. DISCUSSION: Gliomas and meningiomas are the most frequent tumors; other tumors are rare. Through a literature review and many illustrations, we discuss epidemiologic, clinical and radiologic characteristics, treatment and course of these uncommon tumors. CONCLUSION: The diagnosis of optic nerve tumors must be considered in cases of anterior or posterior progressive optic neuropathy. Treatment must be a compromise between effective treatment of the tumor and preservation of visual function. Decisions are made through multidisciplinary consultations, in which the role of the ophthalmologist is crucial for the diagnosis and success of the treatment.

Combination chemotherapy and radiation therapy in lung cancer.

This report outlines the principles and application of chemoirradiation in bronchogenic carcinoma. The emphasis is on the timing of treatment in small cell lung cancer and the Radiation Therapy Oncology Group trial in non-small cell lung cancer. The purpose of this report is to provide a framework for future trials.

Phase II trial of etoposide, cisplatin, continuous infusion 5-fluorouracil, and simultaneous split-course radiation therapy in stage III non-small-cell bronchogenic carcinoma.

Survival in patients with locally advanced, non-small-cell lung cancer (NSCLC) is relatively short, despite treatment with surgery or radiation. A phase II study of simultaneous continuous infusion 5-fluorouracil and split-course radiation with or without surgery has shown possible improvement in median survival compared with that observed in trials of radiation alone. Past success with etoposide plus cisplatin in NSCLC has led to the addition of etoposide to the 5-fluorouracil plus cisplatin plus radiation combination. Twenty-four stage III NSCLC patients were treated with this three-drug regimen, and a 74% clinical partial remission rate was observed. Thoracotomy was done in eight of these patients; subsequent histologic examination of the resected specimen revealed no residual tumor in four patients (50%) and only microscopic foci of tumor in two patients (25%). Major toxicities were leukopenia, nausea, and vomiting. Median leukocyte nadir was 2,900/mm3. A leukocyte count less than 1,000/mm3 was observed in two of 24 patients (8%), one of whom expired from progressive pneumonia. All patients experienced nausea and vomiting, which were classified as moderate in three patients (12%) and severe in four (16%). Moderate to severe esophagitis, dermatitis, and pneumonitis were not observed. Median progression-free interval and median survival were not reached after a median follow-up of 163 days.

Implications of lung corrections for dose specification in radiotherapy.

The influence of taking into account the lung density in the calculation of the dose distributions was examined for a group of 23 patients with bronchus carcinoma. Anatomical information and electron densities were available by means of CT scans. All calculations were made for cobalt-60 gamma rays using a patient specific multiple field irradiation technique. The effect of lung tissues for the dose distributions was calculated using a generalization of Batho's method. All patients entered into this study were planned to receive a minimum tumor dose of 60 Gy, calculated without correction for lung density. The actual dose in each patient was recalculated with lung correction. In the group of patients the corrected minimum tumor dose varied between 63 Gy and 77 Gy (105-128%). The calculated homogeneity of the dose in the target area and the dose to surrounding normal tissues are also affected by lung correction. For different radiation techniques and different methods of dose specification, the interrelation between corrected and uncorrected dose is presented in tables. The impact of lung correction on the uncorrected dose schedules that are commonly used in the treatment of patients with lung cancer is discussed.

Initial experience with a practical hyperfractionated accelerated radiotherapy regimen.

This paper presents early results of a trial of a three-fractions-per-day (TID) regimen that is more convenient to schedule than the Continuous Hyperfractionated Accelerated Radiotherapy (CHART) protocol currently being tested in Europe. The treatment schedule used in the CHART regimen has been modified from 36 fractions of 1.5 Gy TID in 12 days to 72 fractions of 1.1 Gy in 24 treatment days, with all fractions delivered during normal working hours. With no weekend treatments, the entire course of radiotherapy is completed in less than 5 weeks. The doses used were determined using the L-Q model, with correction for incomplete repair between fractions and for accelerated repopulation of cancer cells. Comparison with historical controls shows statistically significant improvements both in CR rates for the primary tumor and in acute toxicity, as measured by reduced treatment interruptions. L-Q model calculations predict that, compared to the highest dose achieved in previous studies without exceeding tolerance, we are able to obtain a 12% increase in bioeffect dose to the primary tumor due to accelerating the treatment. An analysis of the potential tumoricidal effectiveness of this new treatment regimen shows that it should be better than several other accelerated fractionation schedules being tested for all values of Tpot. For short Tpot times, the advantage may be as much as one log cell kill, corresponding to a 10-15% potential improvement in local control.

Endobronchial radiation therapy (EBRT) in the management of lung cancer.

Between October 1987 and November 1988, 19 endobronchial Iridium-192 line source placements were attempted in 17 patients with advanced incurable lung cancer. Approximately 30 Gy was delivered to the endobronchus using a low dose rate (LDR) afterloading technique delivering a mean dose of 70 cGy/hr at 5 mm. Improvement in subjective symptoms was noted in 67% of evaluable patients whereas objective responses defined by chest X ray and bronchoscopy were noted in 26% and 60%, respectively. No significant morbidity was observed. The radiation exposure to health care workers was low ranging from 10 to 40 mRem per treatment course with most of the staff receiving less than 10 mRem per treatment course (minimal detectable level 10 mRem). The results of this series are compared with selected series using low dose rate as well as intermediate dose rate (IDR) and high dose rate (HDR) endobronchial radiation therapy (EBRT). Based on bronchoscopic responses from the selected series reviewed, both HDR low total dose per treatment (range 7.5-10 Gy) and LDR high total dose per treatment (range 30-50 Gy) are effective in palliating the vast majority of patients with endobronchial lesions. Intermediate dose rate is also effective using fractions similar to high dose rate but total dose similar to low dose rate. The efficacy of endobronchial radiation therapy in the palliative setting suggest a possible role for endobronchial radiation therapy combined with external beam irradiation with or without chemotherapy in the initial management of localized lung cancer. Defining the optimal total dose, dose rate, and the exact role of endobronchial radiation therapy in the management of lung cancer will require large cooperative trials with standardization of techniques and definitions.

The effect of arterial oxygen content on the results of radiation therapy for epidermoid bronchogenic carcinoma.

Anemia is believed to be an important prognostic factor in treating cancer patients by radiation therapy. One possible explanation for this is tumor oxygenation. With respect to tumor oxygenation, the arterial oxygen content (CaO2) may be of more importance than the hemoglobin (Hb) level. This study shows the relationship between the CaO2 and tumor response to radiation therapy. Forty-two patients with epidermoid bronchogenic carcinoma, treated by irradiation alone between April 1982 and March 1986, were reviewed. Regression of the tumor after radiation therapy was calculated as a percent change in the tumor area. Arterial oxygen partial pressure (PaO2), Hb level, and percent oxygen saturation of Hb in arterial blood (SaO2) were measured within 2 weeks of commencement of radiation therapy and the CaO2 was calculated. The rank correlation coefficients between the maximum percent regression of the tumor and the PaO2, the Hb level and the CaO2 were 0.36, 0.34, and 0.46, respectively. Statistical analyses of the data indicate that the group of patients with CaO2 over 14.5 ml/dl exhibited greater tumor regression and longer survival periods than the group of patients with CaO2 below 14.5 ml/dl. Similarly patients with PaO2 over 90 mmHg or Hb level over 11 g/dl, exhibited significantly greater tumor regression and longer survival periods than those with PaO2 below 90 mmHg and Hb level below 11 g/dl. There were no significant differences in the length of survival periods with respect solely to the Hb level or the PaO2. It was concluded that the CaO2 is more important than the Hb level in determining tumor response to radiation therapy. This is considered as important indirect evidence of the existence of hypoxic fractions of cells in human tumors.

Radiation myelitis and survival in the radiotherapy of lung cancer.

A previous survey of patients who survived more than 6 months after radiotherapy for carcinoma of the bronchus using a 6 fraction regimen revealed a considerable incidence of radiation myelitis. In a further survey, in which the data bank has been increased from a total of 303 to 754 cases, analyses have confirmed that radiation myelitis occurs once a threshold dose of 33.5 Gy to the spinal cord has been reached. The incidence was positively related to the hemoglobin concentration, but not to the blood pressure at the time of radiotherapy. In the same group of patients survival was positively related to radiation dose, the hemoglobin concentration, and the systolic blood pressure. In other patients who were treated with 6 fractions, but who received a lower minimum tumor dose, either because this was planned or as a result of cord shielding, no relationship was shown between survival and radiation dose, hemoglobin concentration and systolic or pulse pressure. Radiosensitivity is dependent upon the oxygen concentration which, in normal tissues, is related to the hemoglobin concentration and in tumor to both the hemoglobin and the systolic blood pressure. The achievement of a threshold radiation dose appears essential before these prognostic factors become relevant.

A new applicator, positionable to the center of tracheobronchial lumen for HDR-IR-192-afterloading of tracheobronchial tumors.

A new bronchial applicator for afterloading irradiation is introduced which can be positioned to the center of the tracheobronchial lumen. The central position in the lumen leads to a clear improvement of dose distribution. The applicator is built on the principle of a coaxial tube. Parts of the outer cover can be expanded to baskets and effect a distance of the radiation source from the bronchial mucosa or tumor surface, and at the same time, expend a relief of extreme contact doses. No obstruction of the respiratory system through the positioning device will be caused. The positionable bronchial applicator seems to be suitable for reducing complications caused through high contact doses and irregular dose distributions and may be able to improve the results of endoluminal radiotherapy.

Prognostic factors of inoperable localized lung cancer treated by high dose radiotherapy.

A retrospective study was made of the results of high dose radiotherapy (greater than or equal to 50 Gy) given to 171 patients with inoperable, intrathoracic non small cell lung cancer from January 1971-April 1973. Local control was dependent on the total tumor dose: after one year local control was 63% for patients treated with greater than 65 Gy, the two year local control was 35%. If treated with less than 65 Gy the one year local control was less than or equal to 40%. Tumor doses correlated with the size of the booster field. If the size of the booster field was less than 100 cm2, the one year local control was 72%; the two year local control was 44%. Local control was also influenced by the performance status, by the localization of the primary tumor in the left upper lobe and in the periphery of the lung. Local control for tumors in the left upper lobe and in the periphery of the lung was about 70% after one year, and about 40% after two years. The one and two years survival results were correlated with the factors influencing local control. The dose factor, the localization factors and the performance influenced local control independently. Tumors localized in the left upper lobe did metastasize less than tumors in the lower lobe, or in a combination of the two. This was not true for the right upper lobe. No correlation between the TNM system, pathology and the prognosis were found.

Evaluation of short-course preoperative irradiation in the treatment of resectable bronchus carcinoma: long-term analysis of a randomized pilot-study.

A randomized pilot-study on patients with resectable non small-cell lung carcinoma was conducted from December 1971 to May 1976 inclusive. Patients were randomly assigned to receive preoperative irradiation to the mediastinum followed by surgery (RT + S), or to be treated by surgery only (SO). A total of 33 patients clinically staged as T1-2, N0, M0 histologically confirmed bronchus carcinoma were entered onto the study. Sixteen patients were assigned to RT + S and 17 patients received SO. There were 3 operative mortalities, all of them in the SO group. A total of 28 patients, 14 in each group are evaluable, with a minimum period of observation of 7 years. Preoperative irradiation consisted of a Telecobalt photon-beam applied to the mediastinum as anterior and posterior portals. The thoracic spine was protected on the posterior portal by a narrow lead block. A total dose of 20 Gy calculated in the mid plane was given in 5 equal fractions each of 4 Gy administered on 5 consecutive days: Monday through Friday; patients were operated on the following Monday after the week-end. Surgical treatment was similar for both groups and consisted of lobectomy or pneumonectomy, depending on the size and site of the primary tumor. Analysis of the survival data showed an absolute crude 5 years survival rate of 58% for patients who received RT + S versus 43% for SO. The corrected actuarial 5 and 10 years survival rates are 78 and 69% for the group that received RT + S, and 67 and 55% for the group treated by SO, respectively. Nineteen patients were treated more than 10 years ago. Four of 8 (50%) treated by RT + S are alive with no evidence of disease (NED), and 3/11 (28%) treated by SO are alive with NED. The median survival period for the group that received RT + S is 72 months versus 30 months for the group treated by SO. Analysis of the adequacy of surgical resection based on histological examination of the operative specimen showed higher incidence of radical resection in the group that received RT + S (57 versus 28.5%). It is concluded that the treatment protocol of preoperative radiation therapy as outlined is well tolerated and the results are encouraging.