In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.
Cancer; Radiation therapy; Linear energy transfer; Cell death.
Despite advances in radiation delivery protocols, exposure of normal tissues during the course of radiation therapy remains a limiting factor of cancer treatment. If the canonical TGF-β/Smad pathway has been extensively studied and implicated in the development of radiation damage in various organs, the precise modalities of its activation following radiation exposure remain elusive. In the present study, we hypothesized that TGF-β1 signaling and target genes expression may depend on radiation-induced modifications in Smad transcriptional co-repressors/inhibitors expressions (TGIF1, SnoN, Ski and Smad7). In endothelial cells (HUVECs) and in a model of experimental radiation enteropathy in mice, radiation exposure increases expression of TGF-β/Smad pathway and of its target gene PAI-1, together with the overexpression of Smad co-repressor TGIF1. In mice, TGIF1 deficiency is not associated with changes in the expression of radiation-induced TGF-β pathway-related transcripts following localized small intestinal irradiation. In HUVECs, TGIF1 overexpression or silencing has no influence either on the radiation-induced Smad activation or the Smad3-dependent PAI-1 overexpression. However, TGIF1 genetic deficiency sensitizes mice to radiation-induced intestinal damage after total body or localized small intestinal radiation exposure, demonstrating that TGIF1 plays a role in radiation-induced intestinal injury. In conclusion, the TGF-β/Smad co-repressor TGIF1 plays a role in radiation-induced normal tissue damage by a Smad-independent mechanism.
Skin changes from ionizing radiation have been scientifically documented since 1902 (Hymes et al., 2006). Ionizing radiation is a widely accepted form of treatment for various types of cancer. Despite the technological advances, radiation skin injury remains a significant problem. This injury, often referred to as radiation dermatitis, occurs in about 95% of patients receiving radiation therapy for cancer and ranges in severity from mild erythema to moist desquamation and ulceration (McQuestion, 2011; Salvo et al., 2010). Ionizing radiation is not only a concern for cancer patients, but also a public health concern due to the potential for and reality of a nuclear and/or radiological event. Recently, the United States has increased efforts to develop medical countermeasures to protect against radiation toxicities from acts of bioterrorism, as well as cancer treatment. Management of radiation dermatitis would improve the therapeutic benefit of radiation therapy for cancer and potentially the mortality expected in any “dirty bomb” attack (Benderitter et al., 2010; Muller and Meineke, 2010). Currently, there is no effective treatment to prevent or mitigate radiation skin injury. This review summarizes “the good, the bad and the ugly” of current and evolving knowledge regarding mechanisms of and treatments for radiation skin injury.
Cancer is a highly complex disease to understand, because it entails multiple cellular physiological systems. The most common cancer treatments are restricted to chemotherapy, radiation and surgery. Moreover, the early recognition and treatment of cancer remains a technological bottleneck. There is an urgent need to develop new and innovative technologies that could help to delineate tumor margins, identify residual tumor cells and micrometastases, and determine whether a tumor has been completely removed or not. Nanotechnology has witnessed significant progress in the past few decades, and its effect is widespread nowadays in every field. Nanoparticles can be modified in numerous ways to prolong circulation, enhance drug localization, increase drug efficacy, and potentially decrease chances of multidrug resistance by the use of nanotechnology. Recently, research in the field of cancer nanotechnology has made remarkable advances. The present review summarizes the application of various nanotechnology-based approaches towards the diagnostics and therapeutics of cancer.
cancer; diagnosis; drug delivery; nanoparticle; nanotechnology; treatment
Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients.
Materials and Methods
The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently.
Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ≥2 radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ≥2 radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), V20, V30, V40, MLDipsi, V20ipsi, V30ipsi, and V40ipsi were associated with grade ≥2 radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ≥2 radiation pneumonitis.
Concurrent chemotherapy, MLD and V30 were statistically significant predictors of grade ≥2 radiation pneumonitis in patients with stage III non-small cell lung cancer undergoing definitive radiotherapy. The cutoff values for MLD and V30 were 16 Gy and 18%, respectively.
Non-small cell lung cancer; Radiation therapy; Radiation pneumonitis; Dosimetric factor
Prostate cancer is the second most commonly diagnosed cancer in American men over the age of 45 years and is the third most common cause of cancer related deaths in American men. In 2012 it is estimated that 241,740 men will be diagnosed with prostate cancer and 28,170 men will succumb to prostate cancer. Currently, radiation therapy is one of the most common definitive treatment options for localized prostate cancer. However, significant number of patients undergoing radiation therapy will develop locally persistent/recurrent tumours. The varying response rates to radiation may be due to 1) tumor microenvironment, 2) tumor stage/grade, 3) modality used to deliver radiation, and 4) dose of radiation. Higher doses of radiation has not always proved to be effective and have been associated with increased morbidity. Compounds designed to enhance the killing effects of radiation, radiosensitizers, have been extensively investigated over the past decade. The development of radiosensitizing agents could improve survival, improve quality of life and reduce costs, thus benefiting both patients and healthcare systems. Herin, we shall review the role and mechanisms of various agents that can sensitize tumours, specifically prostate cancer.
Cancer; Prostate; Radiation; Radiosensitizer
Human exposure to sources of radiation as well as the use of radiation-derived therapeutic and diagnostic modalities for medical reasons has been ongoing for the last 60 years or so. The carcinogenetic effect of radiation either due to accidental exposure or use of radiation for the treatment of cancer has been undoubtedly proven during the last decades. The role of radiation therapy in the treatment of patients with prostate cancer is constantly increasing as less-invasive treatment modalities are sought for the management of this widely, prevalent disease. Moreover the wide adoption of screening for prostate cancer has led to a decrease in the average age that patients are diagnosed with prostate cancer. Screening has also resulted in the diagnosis of low-grade, less-aggressive prostate cancers which would probably never lead to complications or death from the disease. Radiotherapy for prostate cancer has been linked to the late occurrence of second malignancies both in the true pelvis and outside the targeted area due to low-dose radiation scatter. Secondary malignancies following prostate irradiation include predominantly bladder cancer and, to a lesser extent, colon cancer. Those secondary radiation-induced bladder tumors are usually aggressive and sometimes lethal. Care should be given to the long-term follow up of patients under radiation therapy for prostate cancer, while the indications for its use in certain cases should be reconsidered.
brachytherapy; prostate cancer; radiation therapy; secondary bladder cancer
Although cancer treatment with radiation can produce high cure rates, adverse effects often result from radiotherapy. These toxicities are manifested as damage to normal tissues and organs in the radiation field. In recognition of the substantial variation in the intrinsic response of individuals to radiation, an effort began approximately 10 years ago to discover the genetic markers, primarily SNPs, which are associated with susceptibility for the development of these adverse responses to radiation therapy. The goal of this research is to identify the SNPs that could serve as the basis of an assay to predict which cancer patients are most likely to develop complications resulting from radiotherapy. This would permit personalization and optimization of the treatment plan for each cancer patient.
genome-wide association studies; personalized medicine; radiogenomics; radiotherapy
The Department of Radiation Therapy of Howard University Hospital was the first to revive (1976) the use of intraoperative radiotherapy, or direct view irradiation, using electron beam (IORTe−) in the United States. Since that time, this pioneering effort has gained both national and international acceptance. Now, many leading centers employ this investigational treatment modality. Recently, a new mode of cancer therapy has been gaining acceptance, namely hyperthermia (the treatment of cancer by heat). Hyperthermia has been shown, both experimentally and clinically, to improve the rate of local control (thermal enchancement ratio [TER]) when combined with radiation therapy in the treatment of cancer. Maximal TER has been observed with simultaneous or immediate application of radiation and hyperthermia for both tumor and normal tissues. Therefore, to achieve maximum therapeutic gain, selective, intraoperative, simultaneous heating and irradiation of the tumor with mechanical retraction of the normal and sensitive structures from the treatment field seems a promising alternative.
There have been no published reports, to the authors' knowledge, on the combination of simultaneous IORTe− with intraoperative hyperthermia (IOHT). To employ this combination in human subjects, several questions must be answered first using animal models, including the technical and practical feasibility, the toxicity and morbidity, as well as the pathologic changes that may arise. The technical aspects of the first animal case, using a mongrel dog, applying simultaneous IORTe− and IOHT are presented.
Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft tissue sarcomas has been observed for hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks for developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation.
second cancers; radiotherapy; retinoblastoma; neurofibromatosis type 1; Li-Fraumeni syndrome; Nevoid Basal Cell Carcinoma Syndrome
Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.
DNA damage; ionizing radiation; cancer therapy; gene expression; mutagenesis
Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000 new cases reported annually in the United States. Due to early detection and advances in therapies, more than 90% of patients will survive 10 years post diagnosis and treatment. Radiation is a treatment option often used to treat localized disease; however, while radiation is very effective at killing tumor cells, normal tissues are damaged as well. Potential side-effects due to prostate cancer-related radiation therapy include bowel inflammation, erectile dysfunction, urethral stricture, rectal bleeding and incontinence. Currently, radiation therapy for prostate cancer does not include the administration of therapeutic agents to reduce these side effects and protect normal tissues from radiation-induced damage. In the current study, we show that the small molecular weight antioxidant, MnTE-2-PyP, protects normal tissues from radiation-induced damage in the lower abdomen in rats. Specifically, MnTE-2-PyP protected skin, prostate, and testes from radiation-induced damage. MnTE-2-PyP also protected from erectile dysfunction, a persistent problem regardless of the type of radiation techniques used because the penile neurovascular bundles lay in the peripheral zones of the prostate, where most prostate cancers reside. Based on previous studies showing that MnTE-2-PyP, in combination with radiation, further reduces subcutaneous tumor growth, we believe that MnTE-2-PyP represents an excellent radioprotectant in combination radiotherapy for cancer in general and specifically for prostate cancer.
Radiation therapy methods have evolved remarkably in recent years which have resulted in more effective local tumor control with negligible toxicity of surrounding normal tissues. However, local recurrence and distant metastasis often occur following radiation therapy mostly due to the development of radioresistance through the deregulation of the cell cycle, apoptosis, and inhibition of DNA damage repair mechanisms. Over the last decade, extensive progress in radiotherapy and gene therapy combinatorial approaches has been achieved to overcome resistance of tumor cells to radiation. In this review, we summarize the results from experimental cancer therapy studies on the combination of radiation therapy and gene therapy.
Radiotherapy continues to be a major treatment for solid tumours and is a cornerstone of modern oncology. The term 'radiation oncology' describes the integration of radiation therapy into the complexity of multi-modal therapy. Over the last ten years the crucial role of radiation therapy as part of multi-modality protocols in cancer care has been documented in numerous Phase III trials. Advances in treatment technology as well as the underlying biology of tumour resistance mechanisms will further strengthen the role of radiation oncology. The scientific role of radiation oncology is reflected by the increase in the number of papers related to radiation oncology in resources like Medline. In order to reflect the growing scientific importance of radiation oncology, radiation physics and radiation biology, we have initiated Radiation Oncology as the first open access journal in the field. Open access allows for a rapid and transparent publication process together with an unequalled opportunity to reach the widest reader spectrum possible.
Ionising radiation therapy is a common treatment modality for different types of cancer and its use is expected to increase with advances in screening and early detection of cancer. Radiation injury to the gastrointestinal tract is important factor working against better utility of this important therapeutic modality. Cancer survivors can suffer a wide variety of acute and chronic symptoms following radiotherapy, which significantly reduces their quality of life as well as adding an extra burden to the cost of health care. The accurate diagnosis and treatment of intestinal radiation injury often represents a clinical challenge to practicing physicians in both gastroenterology and oncology. Despite the growing recognition of the problem and some advances in understanding the cellular and molecular mechanisms of radiation injury, relatively little is known about the pathophysiology of gastrointestinal radiation injury or any possible susceptibility factors that could aggravate its severity. The aims of this review are to examine the various clinical manifestations of post-radiation gastrointestinal symptoms, to discuss possible patient and treatment factors implicated in normal gastrointestinal tissue radiosensitivity and to outline different mechanisms of intestinal tissue injury.
Radiation enteritis; Radiation proctitis; Symptoms; Pathophysiology; Risk factors
Recent global radiation fears reflect the urgent need for a new modality that can simply determine if people are in a radiation risk of developing cancer and other illnesses. Ultraviolet (UV) radiation has been thought to be the major risk factor for most skin cancers. Although various biomarkers derived from the responses of human cells have been revealed, detection of these biomarkers is cumbersome, probably requires taking live human tissues, and varies significantly depending on human immune status. Here we hypothesize that the reaction of Propionibacterium acnes (P. acnes), a human resident skin commensal, to UV radiation can serve as early surrogate markers for radiation risk because the bacteria are immediately responsive to radiation. In addition, the bacteria can be readily accessible and exposed to the same field of radiation as human body. To test our hypothesis, P. acnes was exposed to UV-B radiation. The production of porphyrins in P. acnes was significantly reduced with increasing doses of UV-B. The porphyrin reduction can be detected in both P. acnes and human skin bacterial isolates. Exposure of UV-B to P. acnes- inoculated mice led to a significant decrease in porphyrin production in a single colony of P. acnes and simultaneously induced the formation of cyclobutane pyrimidine dimers (CPD) in the epidermal layers of mouse skin. Mass spectrometric analysis via a linear trap quadrupole (LTQ)-Orbitrap XL showed that five peptides including an internal peptide (THLPTGIVVSCQNER) of a peptide chain release factor 2 (RF2) were oxidized by UV-B. Seven peptides including three internal peptides of 60 kDa chaperonin 1 were de-oxidized by UV-B. When compared to UV-B, gamma radiation also decreased the porphyrin production of P. acnes in a dose-dependent manner, but induced a different signature of protein oxidation/de-oxidation. We highlight that uncovering response of skin microbiome to radiation will facilitate the development of pre-symptomatic diagnosis of radiation risk in a battlefield exposure, nuclear accidents, terrorist attacks, or cancer imaging/therapy.
In the past two decades, the increasing ability of radiation to control local tumors in many organs, including the breast, has been well documented. In the past five years, the use of chemotherapy has also assumed a major role in treating micrometastases in breast cancer in selected premenopausal and postmenopausal patients. These two developments have forced a reappraisal of local modalities in the treatment of breast cancer.
Even before the advent of chemotherapy it was known that mastectomy alone was not successful in providing local control and thus adjunctive irradiation when axillae were histologically positive has been used to substantially reduce local recurrence rate. Studies now show that excisional biopsy followed by definitive irradiation accomplishes essentially the same local control, stage by stage, as mastectomy with adjunctive radiation therapy in selected cases. Also, similar five- and ten-year survival rates have been obtained in all recent series.
Irradiation appears to be at least comparable with mastectomy for control of cancer of the breast, but with better functional and cosmetic results.
The incidence of head and neck squamous cell carcinoma (HNSCC) has been gradually increasing over the last three decades. Recent data have now attributed a viral aetiology to a subset of head and neck cancers. Several studies indicate that oral human papillomavirus (HPV) infection is likely to be sexually acquired. The dominance of HPV 16 in HPV+ HNSCC is even greater than that seen in cervical carcinoma of total worldwide cases. Strong evidence suggests that HPV+ status is an important prognostic factor associated with a favourable outcome in head and neck cancers.
Approximately 30 to 40% of HNSCC patients with present with early stage I/II disease. These patients are treated with curative intent using single modality treatments either radiation or surgery alone. A non-operative approach is favored for patients in which surgery followed by either radiation alone or radiochemotherapy may lead to severe functional impairment. Cetuximab, a humanized mouse anti-EGFR IgG1 monoclonal antibody, improved locoregional control and overall survival in combination with radiotherapy in locally advanced tumours but at the cost of some increased cardiac morbidity and mortality.
Finally, the improved prognosis and treatment responses to chemotherapy and radiotherapy by HPV+ tumours may suggest that HPV status detection is required to better plan and individualize patient treatment regimes.
Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects.
Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments.
Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects.
After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.
Curative therapy for childhood cancer has dramatically improved over past decades. Therapeutic radiation has been instrumental in this success. Unfortunately, irradiation is associated with untoward effects, including stroke and other cerebrovascular disease (CVD). The Children’s Oncology Group (COG) has developed guidelines for screening survivors at risk for persistent or late sequelae of cancer therapy.
This review summarizes the pathophysiology and relevant manifestations of radiation-induced CVD and outlines the specific patient groups at risk for early-onset stroke. The reader will be alerted to the availability of the COG recommendations for monitoring, and, when applicable, specific screening and treatment recommendations will be highlighted.
A multidisciplinary task force critically reviewed the existing literature and scored the evidence to establish the current COG guidelines for monitoring health of survivors treated with head and neck irradiation.
Previous head and neck exposure to therapeutic radiation is associated with latent CVD and increased risk for stroke in some patient groups. Common manifestations of radiation-induced CVD includes steno-occlusive disease, moyamoya, aneurysm, mineralizing microangiopathy, vascular malformations, and strokelike migraines.
Risk for stroke is increased in survivors of pediatric CNS tumors, Hodgkin lymphoma, and acute lymphoblastic leukemia who received radiation to the brain and/or neck. As the population of survivors ages, vigilance for stroke and cerebrovascular disease needs to continue based on specific exposures during curative cancer therapy.
= acute lymphoblastic leukemia;
= Childhood Cancer Survivor Study;
= confidence interval;
= Children’s Oncology Group;
= cerebrovascular disease;
= neurofibromatosis type I;
= radiation therapy.
Medical records of patients with carcinoma of the esophagus who received various forms of therapies at our institution, including radiation treatment and chemotherapy with/without surgery, were retrospectively reviewed to examine the outcomes and effects of concomitant multi-modality treatment as well as survival benefits experienced at a single institution over the past decade.
All records of esophageal cancer patients seen and treated at this institution over the past decade were analyzed to assess the predictability of outcomes based on treatment administered. Radiation Therapy: Patients received an average dose of 4500 cGy (range, 3000 – 5400 cGy) to the tumor bed using conformal radiation therapy technique with megavoltage radiation therapy machine. Chemotherapy: Patients received systemic concurrent chemotherapy with a multi-drug regimen of 5-fluorouracil, cisplatin, and etoposide, along with radiation therapy. Surgical Therapy: Patients were re-staged following completion of concurrent chemoradiotherapy to determine feasibility of surgical treatment. Appropriate surgical candidates underwent surgery and received neoadjuvant combined chemoradiotherapy.
The incidence of esophageal cancer at this institution tends to be gradually increasing, at a rate of almost 25% in a decade (7–8 cases vs. 9–10 cases/year in early vs. recent years of the decade). Compared to the early part of the decade, the age of patients now tend to be older (60 – 80 years old). The distribution of histologic types also showed a remarkable shift: squamous type was more prevalent than adenocarcinoma in the early part of the decade, whereas adenocarcinoma histology is more common in recent years. There appears no significant difference in survivals between squamous cell and adenocarcinoma histology. Patient age was not a significant prognostic factor. Data from this study also confirmed higher response rates to combined chemoradiotherapy than to radiation therapy alone. However, it is difficult to make definitive conclusions on the role of surgery in this small retrospective study.
This retrospective study revealed interesting findings: esophageal cancers are being seen in more older patients as compared with previous years and the major histologic type is now adenocarcinoma (70–80%). In addition, combined chemoradiotherapy prolongs survival compared with radiotherapy alone in patients with esophageal cancer. However, the positive role of surgery in multi-modality therapy cannot be confirmed in this study. Further details will be discussed.
Prostate cancer treatment is a controversial topic amongst physicians and patients alike. Radical therapies such as prostatectomy and whole gland radiation offer the best outcomes in terms of oncologic efficacy, but the decision to undergo treatment must be weighed against its potential morbidity. Over the past decade, the concept of focal therapy for prostate cancer has been introduced as a potential method of achieving oncologic control with a lesser degree of morbidity. Focal therapy refers to isolated ablation of a tumor focus with sparing of uninvolved, surrounding tissue. While it remains in the early stages of development, considerable research is underway that will help determine the optimal method of achieving this goal. Current areas of investigation include appropriate candidate selection, lesion identification, modality of treatment, and follow-up strategies.
cryotherapy; focal therapy; high-intensity focused ultrasound (HIFU); histoscan; prostate cancer
Paraneoplastic syndrome (PNS) related to lung cancer is very common. However, the syndrome of inappropriate anti-diuretic hormone secretion (SIADH) is rare in non-small cell lung cancer (NSCLC). We are reporting the case of a 58-year-old female presenting with dyspnea, cough, weight loss, digital clubbing, and one week of haemoptysis. CT showed a mediastinal mass completely encasing her superior vena cava, causing significant narrowing of the trachea and right mainstem bronchus. Bronchoscopy and biopsy identified a non-resectable NSCLC. Palliative radiation therapy was initiated. The day after her first radiation treatment, the patient developed asymptomatic hyponatremia, confirmed to be SIADH by laboratory evaluation. NSCLC-associated SIADH has been reported only thrice over the past two decades and never following radiation therapy with clinical improvement. The patient was discharged home on fluid restriction after her respiratory status improved to continue outpatient radiation and chemotherapy. SIADH in the setting of NSCLC is discussed.
Intensity modulated radiation therapy (IMRT) has revolutionized radiation treatment for head and neck cancers (HNC). When compared to the traditional techniques, IMRT has the unique ability to minimize the dose delivered to normal tissues without compromising tumor coverage. As a result, side effects from high dose radiation have decreased and patient quality of life has improved. In addition to toxicity reduction, excellent clinical outcomes have been reported for IMRT. The first part of this review will focus on clinical results of IMRT for HNC.
Tumor hypoxia or the condition of low oxygen is a key factor for tumor progression and treatment resistance. Hypoxia develops in solid tumors due to aberrant blood vessel formation, fluctuation in blood flow and increasing oxygen demands for tumor growth. Because hypoxic tumor cells are more resistant to ionizing radiation, hypoxia has been a focus of clinical research in radiation therapy for half a decade. Interest for targeting tumor hypoxia have waxed and waned as promising treatments emerged from the laboratory, only to fail in the clinics. However, with the development of new technologies, the prospect of targeting tumor hypoxia is more tangible. The second half of the review will focus on approaches for assessing tumor hypoxia and on the strategies for targeting this important microenvironmental factor in HNC.
Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an integral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, cardiac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threatening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic alterations in tumors and the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumor or normal tissue, leading to improvements in efficacy.
heat shock proteins; radiotherapy; hyperthermia; cancer; hypoxia