Purpose: Adaptive planning is often needed in lung cancer proton therapy to account for geometrical variations, such as tumor shrinkage and other anatomical changes. The purpose of this study is to present our findings in adaptive radiotherapy for lung cancer using uniform scanning proton beams, including clinical workflow, adaptation strategies and considerations, and toxicities.
Methods: We analyzed 165 lung patients treated using uniform scanning proton beams at our center. Quality assurance (QA) plans were generated after repeated computerized tomography (CT) scan to evaluate anatomic and dosimetric change during the course of treatment. Plan adaptation was determined mutually by physicists and physicians after QA plan evaluation, based on several clinical and practical considerations including potential clinical benefit and associated cost in plan adaption. Detailed analysis was performed for all patients with a plan adaptation, including the type of anatomy change, at which fraction the adaption was made, and the strategy for adaptation. Toxicities were compared between patients with and without plan adaptation.
Results: In total, 32 adaptive plans were made for 31 patients out of 165 patients, with one patient undergoing adaptive planning twice. Anatomy changes leading to plan adaptation included tumor shrinkage (17), pleural effusion (3), patient weight loss (2), and tumor growth or other anatomy change (9). The plan adaptation occurred at the 15th fraction on average and ranged from the 1st to 31st fraction. Strategies of plan adaptation included range change only (18), re-planning with new patient-specific hardware (9), and others (5). Most toxicities were Grade 1 or 2, with dermatitis the highest toxicity rate.
Conclusion: Adaptive planning is necessary in proton therapy to account for anatomy change and its effect on proton penetration depth during the course of treatment. It is important to take practical considerations into account and fully understand the limitations of plan adaptation process and tools to make wise decision on adaptive planning. USPT is a safe treatment for lung cancer patients with no Grade 4 toxicity.
Lung cancer is the leading cause of cancer-related deaths worldwide, and almost accounts for 20% of these deaths, however, the cure rate is less than 10% . Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer , but fewer than 15% of individuals diagnosed with NSCLC can survive for more than 5 years, which poses a great threat to the patient’s life and health . Recently, the incidence of lung cancer keeps dynamically growing, but more than 75% of patients at diagnosis has appeared local development or metastasis, missing the best period of surgery. Moreover, despite surgical treatment is the optimal choice for early-stage NSCLC patients, 30%-40% of patients with NSCLC develop tumor recurrence in a short time. Therefore, improving the prognosis of patients with lung cancer and predicting the long-term survival of patients is of particular importance . At present, tumor and node metastasis (TNM) staging system, clinicopathological characteristics, visceral pleural invasion and marginal status are used to predict the disease progression and overall survival of NSCLC patients. There is no index which is stable, effective, reliable and less harmful to assess prognosis, predict recurrence risk and overall survival.
The presence of an incidental finding, defined as an abnormality which is unrelated to the initial scanning indication, is widely increases due to the access to new devices and imaging modalities. This growing number of incidental findings can lead to additional medical care including unnecessary tests nevertheless, in a minority of patients, can lead to diagnosis of an important and unexpected condition that could be crucial for the patient. We reported three cases in which nuclear medicine imaging, performed for different reasons and showed a relevant and unexpected pathology. In the case 1, a bone scan, performed in a 66 aged woman for breast cancer staging, allowed the diagnosis of a uterine fibroma. In the case 2, a HMPAO labeled-WBC scintigraphy performed because of a suspect of osteomyelitis, showed a remarkable heart-shaped photopenic area, highly suggestive of cardiac global dilatation. In the case 3, a 62 aged man referred to bone scintigraphy for the staging of recent diagnosed lung cancer. The bone scan allowed the diagnosis of a meningioma. Therefore, the occurrence of incidental findings could lead to reveal relevant abnormalities for the diagnostic pathway.
Background: Pulmonary fibrosis is a clinical problem with an enigmatic etiology with no effective therapy. Current therapies for lung fibrosis are ineffective for progression of lung fibrosis and preventing respiratory failure.
Objectives: The aim of this study is to explore the expression of Desmin, α-smooth muscle actin (α-SMA) and the telomerase subunit: human telomerase reverse transcriptase (h-TERT) in a spectrum of lung tissue samples consist of lung fibrosis, lung cancer, and healthy controls.
Materials and Methods: The expression of Desmin, α-SMA and hTERT were studied in samples of 15 pulmonary fibrosis samples, 16 samples of lung cancer and 14 healthy controls investigated. We evaluated Desmin, α-SMA as well as the expression of components of telomerase (TERT), by methods: RNA Extraction and cDNA synthesis, Real-Time quantitative PCR, Immunohistochemistry, all prepared from lung tissue paraffin blocked.
Results: α-SMA marker detected 1(8.3%) of healthy control and 11(91.7%) of lung fibrosis samples. The difference between groups was significant (p<0.001). Also the difference between healthy control 1(6.7%) and lung cancer 14 (93.3%) for α-SMA marker was a significant (P<0.001). It was a significant difference between healthy control and lung cancer for TERT expression (P=.005). TERT was not positive in any sample of neither healthy control nor lung fibrosis. For TERT, it was a significant difference between lung fibrosis and lung cancer by Fisher’s Exact Test (P=.004). Expression of TERT and α-SMA between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was not statistically significant (P=.700, P=0758), respectively.
Conclusions: We recommend more investigation to regard α-SMA, Desmin in patients with lung fibrosis and follow them for possible cancer risk. Also, more study is needed to regard TERT as a marker in lung cancer. Assessment of these markers may have future implication to explain the same way of pathogenesis and carcinogenesis of fibrosis and cancer and for prevention or treatment
Today, there is a considerable increase in localizing adrenal bulks with the bringing radiologic diagnosis methods having high technology into use and improvement in diagnostic tests. Adrenal glands are vital tissues for the organism due to the hormones they secrete. Death is a natural result in the absence of adrenal cortex. Adrenal bulks can be seen with different clinical, laboratory and radiological data. These bulks are often benign and rarely malign. They can be functional or non-functional. Major treatment methods used fort he treatment of adrenal gland primary tumors or metastases are surgery, arterial embolisation, chemical ablation, radiofrequency ablation and radiotherapy [1-4].
Adrenal glands are one of the metastatic fields. In wide autopsy series, adrenal metastasis has been determined between the rates of 13-17% . While unilateral metastasis is common, bilateral metastasis’ rate of incidence is between 4-20%. It has been stated that lung (35%), gastric (14%), esophageal (12%) and hepatobiliary (10%) primary carcinomas adrenal metastasis are prevalent most frequently . Curative treatments are tested on patients having cancer with oligo metastasis limited with adrenal gland and primary source is under control because of the expectation of long-term survival, and the surgery is the first choice. These bulks can be treated with open and laparoscopic surrenalectomy in a curative way. It was reported in studies that overall survival was longer in resection of clinically isolated adrenal metastases when compared with nonsurgical therapy (including RFA, external beam radiotherapy, arterial embolization, radioembolization, chemical ablation, and cryoablation) [1,2,5,7]. Lo et al., found one-year survival as 73% and two-year survival as 40% in their study conducted on 52 patients having curative resection for solitary adrenal metastasis . Tanvetyanon et al., demonstrated 5-year survival rates of 25% following resection of isolated synchronous adrenal metastases and reported 26% after resection of metachronous adrenal metastases in their study conducted on NSCLC patients developing solitary adrenal metastasis . Conducted studies revealed that the rate of complication was 9-20% in patients having adrenalectomy for solitary adrenal metastasis [2-4,7].
In recent years, the use of radiotherapy, which is a treatment modality as effective as surgical resection, has become prevalent for the management of oligometastases. Today, three different modalities have been tested in the radiotherapy treatment of adrenal gland metastases. In the first one, total 50 Gy treatment dose with 3D-CRT as daily 2 Gy fraction dose is given . The second one is IMRT implementations for adrenal gland metastases but it isn’t thought as suitable according to Practice Guidelines for Neuroendocrine Tumors published by NCCN in 2010. The third radiotherapy modality is stereotactic body radiotherapy (SBRT). SBRT implementations have started to be preferred today since they are completed in a few fractions in addition to that they show close results to surgery for primary tumors and metastases. Holy et al., implemented SBRT to patients having 13 solitary adrenal metastases with NSCLC at 5 fractions and between 20 and 40 Gy total doses. They found disease-free survival as median 12 months, overall survival as median 23 months and local control rate as 77% . In SBRT implementations for different cancer types determined 30 adrenal metastases, Chawla et al., reported the rates of one-year survival, local control and distant metastasis as 44%, 55% and 13% respectively . In Casamassima et al.,’s study on this issue, the rate of two-year local control was found as 90% . Second degree toxicity was seen in none of the above mentioned studies according to the RTOG toxicity classification. Wardak et al., reported that the patient having lung cancer that they implemented SBRT for bilateral adrenal metastases developed adrenal insufficiency depending on SBRT . Ippolito et al., Reported that adrenal insuffiency may be due to both the tumor and the local treatment . Incidence of symptomatic adrenal insufficiency were reported 4% [2,13]. Casamassima et al and Onishi et al studies, two grade 2 adrenal insuffiencies were reported [11,14].
Consequently, when all these data were evaluated, it is seen that SBRT use has gradually become prevalent for patients not suitable for surgery because of comorbid disease, for patients having oligometastatic cancer that are not suitable for surgery since it has vital risk to resect or that refuse surgery. However, it hasn’t been clear yet that local control will be provided with how many total doses and which fraction schema. There is no agreement on the examination of the adrenal hormone axes because of the short length of life. Besides, it should be kept in mind that adrenal insufficiency can develop in patients implemented SBRT because of bilateral adrenal metastasis developing as synchronous or metachronous. The hormone levels of these patients need to be followed. More researches should be done to lighten this matter.
Chemotherapy is one of the main treatment options for cancer. However, chemotherapeutic agents usually suffer from poor pharmaceutical properties that restrict their use. Targeted therapy drugs have been developed to specifically target changes in cancer cells that help these cells to grow. Such drugs often work when standard chemotherapeutic drugs do not, they often have less severe side effects and they are most often used for advanced cancers. The objective of this article is to give an overview about the 16 FDA-approved targeted therapy drugs to treat non-small cell lung cancer.
Tobias R Overbeck*, Stefan HP Wenleder*, Bernhard C Danner, Wolfgang Körber, Karin Toepelt, Bernhard Hemmerlein, Christina Perske, Markus Falk, Markus Tiemann, Claudia Tomala, Elke Stitz and Frank Griesinger
Background: In 2004 we started a phase II trial in non-small lung cancer (NSCLC), stage III, with erlotinib followed by a combination with a platinum-based doublet in unselected patients to identify molecular subgroups benefitting from an EGFR targeting approach.
Patients and methods: Induction with erlotinib (E, 150 mg, d1-42) was followed by three cycles of gemcitabine (G, 1250 mg/m², d1+d8, q3w) and cisplatin (P, 80 mg/m², d1, q3w). Patients with at least stable disease after E were treated with a GP + E combination. Induction was followed by surgery and radiation. The trial was conducted as a prospective, multi-center, open label, exploratory phase II study to determine pathological response rate (pRR), as well as secondary endpoints disease free survival (DFS) and overall survival (OS).
Results: Of 38 prescreened patients 16 were included in the main study. Due to slow recruitment the study had to be terminated early. Combination of E and GP was well tolerated, surgery was feasible after induction therapy in 12 of 16 patients, 7/12 (58%) patients had a major pathological response (MPR). Median overall survival for patients with MPR was 57.7 months (confidence interval (CI), 37.4 to 78.0; n = 7) and for patients without MPR 11.9 months (CI, 6.4 to 17.4; n = 5). 2/16 patients had an epidermal growth factor receptor (EGFR) mutation.
Conclusion: Before discovery of distinct molecular mechanisms in NSCLC our study was an attempt to identify clinical and pathological subgroups that would benefit from E induction. Two patients with an EGFR mutation were identified. MPR was a predictor of long term disease free and overall survival.
Despite the fact, that lung cancer is more common among older smoking men, however it may also develop among young women without a smoking anamnesis. We report here a history of a non-smoking woman, 40 years old, with a diagnosis of lung adenocarcinoma at IV stage. Despite the fact, the woman received three lines of palliative chemotherapy, the disease progressed. After the sample of the tumor was tested by genetic approach, ROS1 mutation was detected, and the patient was treated with a ROS1 inhibitor, Crizotinib. Sharp improvement was observed already after the first week of treatment. After one-month adenocarcinoma shrink, and specific supraclavicular lymph nodes disappeared. Unfortunately, due to problems with financing the treatment was stopped, after what the disease began to progress rapidly, and the patient died after a month due to brain metastasis. This case is noteworthy also because the patient was first diagnosed a thrombophilia with thrombi present in deep calf veins, left heart ventricle and lungs Adenocarcinoma was discovered occasionally when during video-assisted thoracoscopic surgery biopsy specimen was taken from suspicious mass in the lower lobe of the right lung. This story reminds us that lung carcinoma may start with a paraneoplastic syndrome, like thrombophilia as in this case and finding of adenocarcinoma of the lung in young, non-smoking persons is indicative for possible ROS1 gene mutation. In such cases early treatment with ROS1 protein-tyrosine kinase inhibitors should be started as soon as possible.
Non-small cell lung cancer is one of the leading causes of cancer-related mortality worldwide. Despite recent advances in adjuvant treatments, surgical resection is basis of treatment. With the development of minimally invasive surgery in thoracic surgery, surgeons work on minimally invasive surgery for advanced stages of lung cancer, previously considered non-operable at all or previously considered non-operable with minimally invasive surgery approach.
Minimally invasive surgical techniques which are routinely used in the surgical treatment of early-stage lung cancer have started to be treated in more complicated and advanced stages of lung cancer. Bilateral anatomic resections, operations after neoadjuvant chemotherapy, bronchial sleeve lobectomies, double sleeve lobectomies, complementary pneumonectomies, and carinal sleeve resections can be performed by minimally invasive methods. The option of video-assisted surgery should be considered with oncological principles at foreground if patients have acceptable lung and cardiac performance conditions with minimal comorbidities.
This study reviews VATS experience in patients with advanced-stage lung cancer worldwide and discusses potential benefits and limitations of using VATS technology to perform thoracic surgery procedures.
Segmentectomy may be applied to all segments; superior segmentectomies (lower lobe superior segments for both lungs), lingulectomies (two segments forming lingulas of upper left lobe) and basal segmentectomies (segments other than superior segment for both lungs). In lung segment resections; segmentectomy has an equivalent morbidity, recurrence and survival rate compared to lobectomy, in patients with stage I lung cancer, tumors smaller than 2 cm and within the segmental anatomical limits. Segmentectomy also contributes more to preserving lung function and exercise capacity than lobectomy. In tumor resection; especially in patients with advanced age, insufficient performance or insufficient cardiopulmonary reserve, 2 cm in diameter and acceptable segmental margins may be provided.
Limited long-term results show oncological results of robotic approach similar to open and VATS approaches. Robotic approach facilitates surgery with more intuitive movements, greater flexibility and high definition, three-dimensional vision. However, high cost and lack of touch sense are main disadvantages of robotic surgery. New studies are needed to assess quality of life, morbidity, oncological results and cost effectiveness. However, considering development of technology in our age and fact that many surgical robot brands will be released in the near future, it is predicted that disadvantages of robotic surgery will be minimized in the near future.
This article reviews experience of segmentectomy in non-small cell lung cancer and discusses benefits and limitations of robotic segmentectomy.
Lung cancer is a major cause of morbidity and mortality worldwide. Metastasis can be seen in many organs in advanced-stage disease. Acral metastasis rate in cancer is quite low. However, because of the direct opening of the arterial circulation, the risk of acral metastasis stem from lung cancer is higher than any other cancers. Although the mechanism is not known exactly, acral metastases occur in dominant extremities. Here, we present a case with lung adenocarcinoma metastasis of the left hand in the second phalanx. We presented this case which is rarely seen in the literature to emphasize acral metastases.
As per report of WHO  (World Health Organization), air pollution (ambient/outdoor and household/indoor air pollution) kills an estimated seven million people worldwide every year largely as a result of increased mortality from stroke, heart disease, chronic obstructive pulmonary disease, lung cancer and acute respiratory infections. Data of WHO shows that 9 out of 10 people breathe air containing high levels of pollutants. World Health Organization is working with countries to monitor air pollution and improve air quality. From smog hanging over cities to smoke inside the home, air pollution poses a major threat to health and climate. More than 80% of people living in urban areas and around 91% of the world’s population live in places where air quality levels exceed WHO limits, with developing and under-developed countries suffering from the highest exposures, both indoors and outdoors . While outdoor air pollution comes from the motor vehicles, burning of fossil fuels and other industrialization activities, indoor air pollution is the result of tobacco smoke and burning fuel for cooking & heating. Furniture and construction materials also emit such pollutants. Both outdoor and indoor air pollution are harmful to the human health.
Purpose: In an aspect of qualitative treatment, this research gathered lung cancer patients’ actual experiences to understand deeply, such as their expectation for treatment results, their difficulties during treatment, and their various requests to their family and medical teams.
Methods: From May to June 2013, semi-structured interviews were conducted with 9 lung cancer patients. Data were collected through a tape-recorded in-depth interview. The analysis of the data was made through the qualitative method.
Results: 124 themes regarding the experience were found. From these 35 concepts, 24 subcategories were emerged. The core category was enduring hardship of the treatment with the hope for full recovery. Six categories included ‘Wishing to be cured but concern about recurrence’, ‘Receiving radiation treatment with pleasure and difficult at the same time’. ‘Being sorry for their family’s full support and trying to stand alone‘, ‘Having confidence in their medical team’, ‘regretting for their old days’, and ‘Wanting to live a long life without illness and pain’.
Conclusion: The results of this study would help oncology nurses to understand the lung cancer patients receiving concurrent chemo-radiotherapy (CCRT) and to develop a quality of life improvement program for physical, psychosocial, and spiritual aspects of nursing.
Advances in metagenomics have facilitated population studies of associations between microbial compositions and host properties, but strategies to minimize biases in these population analyses are needed. However, the effects of storage conditions, including freezing and preservation buffer, on microbial populations in fecal samples have not been studied sufficiently. In this study, we investigated metagenomic differences between fecal samples stored in different conditions. We collected 46 fecal samples from patients with lung cancer. DNA quality and microbial composition within different storage Methods were compared throughout 16S rRNA sequencing and post analysis. DNA quality and sequencing results for two storage conditions (freezing and preservation in buffer) did not differ significantly, whereas microbial information was better preserved in buffer than by freezing. In a metagenomic analysis, we observed that the microbial compositional distance was small within the same storage condition. Taxonomic annotation revealed that many microbes differed in abundance between frozen and buffer-preserved feces. In particular, the abundances of Firmicutes and Bacteroidetes varied depending on storage conditions. Microbes belonging to these phyla differed, resulting in biases in population metagenomic analysis. We suggest that a unified storage Methods is requisite for accurate population metagenomic studies.
Systemic arterial air embolism (SAAE) is a rare but serious complication of CT-guided hook wire localization of pulmonary nodule usually with catastrophic and poor outcome. Hook wire needle localization is done pre-operatively by placing wire around or into the pulmonary nodule to provide the thoracic surgeon accurate location guidance of the target nodule for Video-Assisted Thoracoscopic Surgery (VATS) wedge resection with safety margins. Physicians should be aware of this possible complication during the procedure in order to rescue the patient promptly as it requires rapid diagnosis and management. We describe a 55-year-old male who underwent a CT-guided hook wire needle localization of left upper lobe lung cancer and left lower lobe pulmonary nodule prior to planned VATS wedge resection who developed altered mental status and bilateral lower extremities paralysis after wire placement was completed. His CT head demonstrated small air embolism in the left occipital area, confirming the diagnosis of cerebral air embolism and follow up CT and MRI of the head revealed multiple areas of brain infarction. In addition, he was diagnosed with anterior spinal cord syndrome (ACS), most likely due to anterior spinal artery ischemia from micro air embolism on the basis of clinical findings but with negative ischemic changes on MRI of the spinal cord. His mental status recovered but he remained paraplegic and transferred to inpatient rehabilitation service.
Cancer metastasis to the pituitary gland is rare, but in most cases, it originates from a late-stage breast tumor or lung cancer. The most common symptoms of metastasis to the pituitary gland are diabetes insipidus and visual disturbance. The common site of metastasis is the posterior portion of the pituitary gland because it is highly vascularized. Metastases to this site represent 1% of all tumors . Metastasis to the pituitary gland is difficult to diagnose by hormonal analysis and magnetic resonance imaging of the brain and requires biopsy for confirmation .
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Department of Neurosurgery, Queen Elizabeth Hospital, Hong Kong
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Muhammad Sarwar Khan
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