5-Alpha Reductase Inhibitors Not Associated with Increased Risk for High-Grade Prostate ca

Men who take the 5-alpha reductase inhibitors (5-ARIs), finasteride and dutasteride, for lower urinary tract symptoms are not at increased risk for high-grade prostate tumors, according to a BMJ study. Since 2011, 5-ARI labels have warned of the increased risk for high-grade prostate cancer. - See more at:

Use of Advanced Technologies in Low-Risk Prostate Cancer on the Rise

The use of advanced treatment technologies for prostate cancer has nearly doubled among men who are least likely to benefit, a JAMA study finds. Researchers examined Medicare data to compare the use of different prostate cancer treatments between 2004 and 2009. Some 56,000 men with new prostate cancer diagnoses were included; advanced treatment technologies were defined as intensity-modulated radiotherapy and robotic prostatectomy. The use of advanced technologies for men with low-risk disease rose from 32% in 2004 to 44% in 2009; among men at high risk for death from other causes within 10 years, the use of these treatments increased from 36% to 57%. Overall, advanced technologies among men unlikely to die from prostate cancer rose from 13% to 24%. The researchers conclude: "Continued efforts to differentiate indolent from aggressive disease and to improve the prediction of patient life expectancy may help reduce the use of advanced treatment technologies in this patient population." ref - http://jama.jamanetwork.com/article.aspx?articleid=1700496

Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis

cancer is increasingly thought of as a chronic disease—about 70% of patients live for at least 5 years after diagnosis. A key question for clinicians is whether the prevalence of mood disorders is significantly different in patients compared with spouses. A second question is whether the prevalence of mood disorders is different in long-term cancer survivors compared with the general population. This study took a form of a systematic review. Search terms- Title=((depressi* or mood or anxious or anxiety)) AND Topic=((long-term or years or months or survivo*) and (control* or healthy or spous* or relative or carer or caregiver or family)) AND Title=((cancer or tumour or tumor or metast* or oncology or palliati* or lymphoma or leukaemia or leukemia or myeloma or bone-marrow transplant)) Results “cancer patients had much the same prevalence of depression as did spouses and healthy controls”. results suggest that after diagnosis of cancer, increased rates of anxiety tend to persist compared with healthy controls, whereas increased rates of depression are less longlasting. Anxiety thus seems more prevalent than the usually tested depression and distress. Thus anxiety scales could be ulitilised more so in practice which may influence QoL, pain and burden on the diagnoses of cancer. limitation is that few studies provided adequate clinical descriptions of functional performance, social support, past history, or stage of disease. Thus, we were unable to adequately examine predictors of anxiety and depression ref http://www.sciencedirect.com/science/article/pii/S1470204513702444

The impact of anti-inflammatory agents on the outcome of patients with colorectal cancer

Inflammation has been implicated in the pathogenesis of many adult malignancies and is now recognised as the seventh “hallmark” of cancer. inflammatory response has been associated with a poorer response to chemotherapeutic agents and an increased risk of toxicity. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), potential chemotherapeutic drugs which may favourably manipulate the inflammatory response in CRC. emerging evidence of as much as a 40% reduction in mortality in patients undergoing curative treatment makes the concept of the use of NSAIDs as adjuvant treatment in high risk disease more compelling. present review examines the clinical evidence supporting the use of NSAIDs, statins and H2RAs in influencing the tumour microenvironment and host inflammatory response in CRC. Aspirin, NSAIDs and COX-2 inhibitors aspirin has also been found to confer a protective effect on the colorectum in patients with Lynch syndrome. 30% risk reduction with aspirin and non-aspirin NSAIDS and a potentially greater reduction with COX inhibitors. The effect is transcient over time, and greater benefit if the patient takes the pills greater than 10yrs, simularily cessation of regular use results in a return to normal population risk for subsequent CRC development. However given the extra side effect profile of adding NSAIDS into someones regime (gastic bleed), prophylactic agents in the general population is deferred until at least the optimal target population is identified. The mechanism of action of these drugs appears to increase in tumour cell apoptosis in association with a decrease in cell proliferation, angiogenesis and metastatic potential. Using COX inhibitors (aspirin) mediates (COX)-mediated synthesis of prostanoids, and in particular prostaglandin E2 (PGE2). PGE2 by COX-2, the inducible form of the enzyme has been shown to have several pro-tumour and immunosuppressant effects. Aspirin at doses that affect COX1 can also increase in platelet activation demonstrated in CRC patients, this might lead to decrease in haematogenous spread. Non Cox independent effects of NSAIDS are said to affect several molecular pathways, i.e. mTOR, PI3K, NF-KB as people with evidence of mutations in these pathways seem to do better with adminsteration of NSAIDS. Furthermore, NSAIDs have been shown to induce expression of MHC class II molecules on the surface of CRC cells, allowing an immune repsonce to occur against cancer cells and also a decrease in immunosuppressive regulatory T-lymphocytes (Treg). The level of inflammation can be measured in patients via blood tests for TNF receptor-2. Sub-analysis of a randomised trial of 5-fluorouracil and leucovorin with or without irinotecan in patients with stage III colon cancer examined the effect of aspirin and COXIBs on recurrence and survival.66 Even after controlling for treatment arm, NSAID use was associated with a 50% reduction in disease recurrence or death. ecreased synthesis of protective prostaglandins via inhibition of COX-2 has been shown to increase tumour radiosensitivity. Statins 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)- statins. results of meta-analyses suggest only a modest effect if any of statins on reducing the incidence of CRC in the general population. How do they decrease cancer? - Mevalonate, the end product of HMG-CoA reductase metabolism and its isoprenoid metabolites are required for the activation of the Ras superfamily of small GTPases by prenylation.78 In turn, these GTPases are crucial for downstream activity of several signal transduction pathways. Also they have a clear anti-inflammatory effect of statins (IL-6). Plus statin therapy has been shown to augment the activity of a number of chemotherapeutic agents, even in resistant cell lines. However most studies offer conflicting results, maybe due to there population variation in individuals and the dosing of statins used. Histamine H2 antagonists. Why? – H2RA- offer inhibition of histamine as a growth factor and inhibition of tumour-endothelial cell adhesion and motility. Furthermore, prolonged H2RA use has been shown to increase the systemic bioavailability of 5-fU. Histamine acts as an autocrine tumour growth factor and has been shown to increase CRC cell proliferation and growth + histamine has also been shown to increase expression of COX-2 and PGE2 as well as vascular endothelial growth factor in cell lines constitutively expressing COX-2. H2RAs may also reduce the metastatic potential of colorectal tumour cells by inhibition of E-selectin expression. H2RAs has been shown to restore circulating levels and activity of T-lymphocyte and NK cell subsets,116 potentially via augmentation of IL-2 and interferon activity in inflamation. Matsumoto and co-workers reported the survival analysis of a multicentre, randomised controlled trial of the effects of cimetidine on adjuvant 5-fluorouracil-induced appetite loss and oesophagitis.119 Interestingly, they found a significant increase in survival for both colonic and rectal cancers at almost 4 years. So far the role of these drugs have yet to be defined for the general population and for the ideal cancer patient in order to reap the most rewards without giving patients over treatment and extra morbidities that are related to long term use of inflammatory inhibitors. Further studies are needed ref

Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial

study showing For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. read more if interested here-

Cabozantinib, TKI, for metastatic castration resistant prostate disease.

For metastatic castration resistant prostate cancer, many new options are becoming available, such as androgen receptor targeted agents such as abiratone, enzalutamide, plus other novel drugs such as sipulecel-T, and cabazitaxel. An oral TKI, called Cabozantinib, has activity against VEGF2 and mesenchymal-epithelial transistion factor (MET)- both of which are expressed in CRPC. A phase II trial, 171 CRPC patients, those with stable disease after one regimen of chemo were randomly assigned to cabozantinib or placebo. Patients on cabozantinib has higher median PFS, 23.9m vs 5.9months. and had better resolution of bone improvements as seen on bone scan. Toxicity of cabozantinib were like other TKI which inc fatigue, weight loss, hand-foot syndrome, which led to reduction of dose in 60% of patients. Due to the striking change in bone scans of phase II patients, Phase III trials are in progress studing affects of cabozantinib vs either mitoxantone and prednisone or prednisone alone in order to access pain and bone scan responses. Ref- Smith D. C., et al. (2013). Cabozantinib in patients with advanced prostate cancer: results of a phase II randomised discontinuation trial. Journal of Clinical Oncology, 31, 412.

Oncology Scan – Gynecological Cancers: New Treatments, Old Treatments, Imaging, and Meta-Analyses

This article covers some new and contending debates into treatment of gynae cancers. Nesvacil et al. Adaptive image guided brachytherapy for cervical cancer: A combined MRI-/CT-planning technique with MRI only at first fraction. Radiother Oncol 2012. gold standard magnetic resonance imaging (MRI) for all brachytherapy fractions. image-guided brachytherapy for cervical cancer in 20 patients, comparing plans based on (1) MRI guidance only with (2) MRI guidance for the first insertion and initial 2 fractions and computed tomography (CT) for the subsequent 2 fractions. The data indicate that on evaluation of the total treatment dose comparing the full MRI planning to the MRI/CT planning method, the MRI/CT planning underestimates the real D90 by 1.5 ± 4.3 Gy. full MRI planning technique was compared with the MRI/CT technique with transfer of data back to MRI anatomy for the “real dose” delivered, the mean D90 difference was smaller by 0.7 ± 5.3 Gy. Comparison studies between CT and MRI have demonstrated the superiority of MRI; however, its adoption worldwide has been hindered by the expense and lack of availability of MRI. Kong et al. Adjuvant radiotherapy for stage I endometrial cancer. Cochrane Database Syst Rev 2012- The results of this meta-analysis reconfirm the effectiveness of EBRT in reducing LRR for women with early-stage endometrial cancer but do not find evidence that EBRT improves overall survival. Results on the implement og EBRT depend on how one evaluates the goals of EBRT, i.e. is local regional recur rate a justified end point use to implement EBRT? Thus much debate over treatment for early stage still exists, Frumovitz et al. Anatomic location of PET-positive aortocaval nodes in patients with locally advanced cervical cancer: implications for surgical staging. Int J Gynecol Cancer 2012. 46 patients who underwent pretherapy positron emission tomography (PET)/CT before definitive radiation/chemotherapy for cervical cancer to access pelvic and para-aortic lymph node involvement according to molecular imaging in patients with stage IB-IV disease. = 93% of patients with PET-positive para-aortic lymph nodes also had pelvic lymph node involvement → a stepwise progression along parametrial structures to pelvic (obturator, external iliac, internal iliac), common iliac node echelons and finally along the para-aortic chain. 7% of patients had para-aortic node involvement without pelvic involvement → alternative pathways may be at play through lymphatic spread along ovarian vessels directly to the upper para-aortic chain. Hoskins et al. Low-stage ovarian clear cell carcinoma: Population-based outcomes in British Columbia, Canada, with evidence for a survival benefit as a result of irradiation. J Clin Oncol 2012. role of abdominal and pelvic RT (APRT) for patients with stage I or II clear cell ovarian cancer. All underwent standardized ovarian cancer surgery followed by 3 (APRT cohort) or 6 (no APRT) cycles of platinum/taxane chemotherapy → 22.5 Gy to the entire peritoneal cavity and an additional 22.5 Gy to the pelvis. APRT as consolidative treatment after standard chemotherapy is feasible and safe and may be associated with improved survival in selected patients compared with chemotherapy alone. clear cell cancer is biologically distinct from other types of ovarian cancer and exhibits different clinical behavior. Clear cell tumors are more likely to be confined to the pelvis. This study shows survival advantage in patients with stage IC or II disease and positive peritoneal cytology or ovarian surface involvement Ref http://www.sciencedirect.com/science/article/pii/S0360301613001077

Palliative Radiotherapy for Bone Metastases: An ASTRO Evidence-Based Guideline

Bone mets = pain, spinal cord compression, hypercalcemia, and pathologic fracture. External beam RT (EBRT) can provide significant palliation of painful bone metastases in 50–80% of patients. single-fraction RT schedules compared with longer courses of palliative RT, single- conveince, longer- lower treatment rate. Relative lack of palliative RT guidelines formulated to date, made ASTRO to convene task force into the options for treating bone mets and what treatment strategy one should use. “PubMed database through December 22, 2009 using the Medical Subject Heading term “Radiotherapy bone metastases,” limiting the results to 1998 through 2009. Of the 4,287 articles originally identified” What fractionation schemes- 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, and a single 8-Gy fraction for patients with previously unirradiated painful bone metastases. Fractionated RT courses have been associated with an 8% repeat treatment rate, whilst single # more convienent. When is single fraction RT appropriate- no data to suggest that a single 8-Gy fraction provided inferior pain relief compared with a more prolonged RT course in painful spinal sites. When should patients receive repeat treatment with RT to spinal lesions causing recurrent pain? Care must be taken when the re-irradiated volume contains the spinal cord, and it might be appropriate to sum the biologically effective doses from the initial and repeat treatment regimens to estimate the risk of radiation myelopathy Surgery and EBRT for spinal cord compression. longer schedules, such as 30 Gy in 10 fractions, have been the most commonly used because the intent will be to eradicate microscopic residual disease rather than relieve symptoms, as surgery decompression cares for the macroscopic disease. Surgical decompression and stabilization plus postoperative RT should be considered for selected patients with single-level spinal cord compression or spinal instability Ref http://www.sciencedirect.com/science/article/pii/S0360301610035777

female pelvic imaging paper

just a quick link to something i found, good for anatomy image interpretatiob possibly?

Cabozantinib in patients with advanced prostate cancer:

Cabozantinib, TKI, for metastatic castration resistant prostate disease. For metastatic castration resistant prostate cancer, many new options are becoming available, such as androgen receptor targeted agents such as abiratone, enzalutamide, plus other novel drugs such as sipulecel-T, and cabazitaxel. An oral TKI, called Cabozantinib, has activity against VEGF2 and mesenchymal-epithelial transistion factor (MET)- both of which are expressed in CRPC. A phase II trial, 171 CRPC patients, those with stable disease after one regimen of chemo were randomly assigned to cabozantinib or placebo. Patients on cabozantinib has higher median PFS, 23.9m vs 5.9months. and had better resolution of bone improvements as seen on bone scan. Toxicity of cabozantinib were like other TKI which inc fatigue, weight loss, hand-foot syndrome, which led to reduction of dose in 60% of paitents. Due to the striking change in bone scans of phase II patients, Phase III trials are in progress studing affects of cabozantinib vs either mitoxantone and prednisone or prednisone alone in order to access pain and bone scan responses. Ref- Smith D. C., et al. (2013). Cabozantinib in patients with advanced prostate cancer: results of a phase II randomised discontinuation trial. Journal of Clinical Oncology, 31, 412.

Age and Comorbidity Considerations Related to Radiotherapy and Chemotherapy Administration

Sixty percent of incident cancer cases and 70% of mortality occurs in individuals over the age of 65 years, this increase may correlate with increased comorbidity burden making treatment decisions more difficult to call. age is a known risk factor for the development of cancer. “Comorbidity in cancer patients refers to other concurrent patient illnesses”. Elderly patients and/or patients with significant comorbidity burden are routinely excluded from randomized controlled trials in order not to potentially affect any postitive results of whatever is being tested. Therefore, clinical trial results may still have limited external validity for many elderly patients. Janssen-Heijnen et al (cited in article) observed survival decrements related to age and comorbidities, with comorbidity having a minimal role in patients with highly aggressive tumors. Other important relevant relationships have been described in the medical literature: 1 Age, comorbidity, functional impairment, and cancer site are all independent contributors to survival time. 2 Comorbidity burden can have a differential impact on survival in cancer populations with different baseline survival rates. 3 Comorbidity and functional status are separate entities within the context of elderly patients and need to be measured individually. 4 Type/intensity of cancer treatment and their related complication patterns can be impacted by both age and comorbidity status. 5 Observed population-based treatment adaptations owing to age and/or comorbidity considerations depend on the cancer site involved. 6 Frequently observed adaptive therapies include less use of surgery when alternative approaches are available (chemoradiation, radiation alone, chemotherapy alone, hormonal therapy), less use of adjuvant radiation and/or chemotherapy after surgery, and increased use of observation strategies where available. 7 Age and comorbidity burden have impacts on both health-related quality of life13 and symptom burden.27 In a population of cancer survivors, younger age was associated with higher symptom burden than older patients. Radiothearpy- the long duration of radical radiation therapy (>5 weeks) and geographic considerations (patient travel time away from home) can play a critical role in patient selection of palliative or best supportive care treatment where a more radical course would be generally indicated. radical or palliative radiotherapy can be a tolerable treatment for elderly patients when comorbidities functional status is assessed and integrated into the treatment plan. Chemo- factors affecting pharmacokinetics/dynamics in increasing age can have important effects on chemotherapy dosing and tolerance include decreased renal function, decreased volume of distribution, decreased liver cytochrome P450 function, decreased gastrointestinal absorption, and decreased bone marrow reserve. A complete patient assessment should include documentation of the patients' chronologic age, estimated physiological age, presence and severity of comorbidities, contraindications to radiotherapy (and chemotherapy), and performance/functional status. “medical optimization of baseline comorbidities before treatment should be considered to optimize patient treatment tolerability and to reduce comorbidity impact and mortality.” Ref- http://www.sciencedirect.com/science/article/pii/S1053429612000471

T-DM1 for Her2 positive breast cancer

FDA approval of antibody drug conjugate T- DM1 (trastuzumab emtansine, Kadcyla), deliverers cytotoxic to its target Her2+ receptor. Phase II studies show from 137 patients, randomly assigned to receive first line trastuzumab + docetaxel (TD), vs TDM1, after median 23month F/U, PFS was signigicany improved compared to TD, 14.2 vs 9.2 months. Together with higher objective response to TDM1 vs TD. TDM1 also associated to lower serious adverse risks. Thus, one may expect the future that TDM1 will replace current treatment for Her2+ metastatic BC who experience disease progression after receiving Trasustmab. Has a favorable safety profile. Clinical trials of using TDM1 in ealier treatment and adjuvant settings with metastatic BC are under way. Ref- Hurvitz et al. Phase II randomized study of trastuzumab Emtansine versus trastuzumab plus docetaxel in patients with Her2+ metastatic Breast cancer. J Clinincal Oncology. 2013. 31, 1157

News

FDA approves two drugs, companion diagnostic test for advanced skin cancer The U.S. Food and Drug Administration today approved two new drugs, Tafinlar (dabrafenib) and Mekinist (trametinib), for patients with advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma, the most dangerous type of skin cancer. Ref http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm354199 Editoral on current colorectal screening- June, The lancet Oncology Screening for pre cancerous polyps maybe one reason why incidence and mortality of colorectal cancer is decreasing. Howvever the lifetime risk of colorectal cancer is only about 5%, "suggests that not all adenomas become cancer, but present techniques cannot reliably predict which polyps will progress and which will regress or remain stable". Pickhardt et al (2013) in same issue, suggest that a volumetric growth characteristic can be used to predict the growth rate of polyps thus if found to be quick growing the patient can proceed to the next clinical stage of treatment, if slow glowing a active monitoring apporaoch can be used. HOwever questions need to be considered in that do these slow growing polps stop or do they flucutate? If these polpys defined as slow growing later become an issue, is delayed removal benefical? The second question relates to the generalisability of these findings to a larger screening population. THis later question regards the rate of patient accural to the CT study done by Pickhardt et al. Thus this editoral of the paper by Pickhardt et al (2013), show that using CT clonoscopy one could personalise medical treatment in preferance to the charactertics of the cellular morphology. ref- http://www.sciencedirect.com/science/article/pii/S1470204513702523 orginal article, Perry J Pickhardt, David H Kim, B Dustin Pooler, J Louis Hinshaw, Duncan Barlow, Don Jensen, Mark Reichelderfer, Brooks D Cash, Assessment of volumetric growth rates of small colorectal polyps with CT colonography: a longitudinal study of natural history, The Lancet Oncology, Available online 7 June 2013, ISSN 1470-2045, 10.1016/S1470-2045(13)70216-X. (http://www.sciencedirect.com/science/article/pii/S147020451370216X)

Targeted Therapies with Chemoradiation in Esophageal Cancer: Development and Future Directions

Human Epidermal Growth Factor Receptor 2 (HER2) HER2, epidermal growth factor receptor, and vascular endothelial growth factor pathways have been most extensively studied in esophagogastric cancers. Neoadjuvant and definitive chemoradiation are effective. This review will first focus on 3 of the most widely studied targeted therapies, trastuzumab (anti-HER2), bevacizumab (anti-vascular endothelial growth factor [anti-VEGF]), and cetuximab (anti-epidermal growth factor receptor [anti-EGFR]) Trastuzumab HER2 overexpression has been found in esophagogastric cancer at rates similar to breast cancer. In a large multi-institutional series. In a study, of patients with HER2-positive gastric or GE cancer were randomized to either trastuzumab and chemotherapy or chemotherapy alone. Median survival was improved with the addition of trastuzumab to chemotherapy from 11.1 to 13.5 months. If the tumor is found to be HER2 positive, patients are randomized to concurrent and maintenance trastuzumab in addition to chemoradiation. Chemoradiation consists of a dose of 50.4 Gy along with weekly carboplatin (AUC 2) and paclitaxel (50 mg/m2). Bevacizumab phase II study, Shah et al12 added bevacizumab to cisplatin and irinotecan and observed a response rate of 65% and a median survival of 12.3 months. In another phase II study, Shah et al13 evaluated bevacizumab in combination with docetaxel, cisplatin, and 5-FU. This regimen yielded a response rate of 67% and an impressive median survival of 16.8 months. Ilson et al18 reported results of preoperative chemoradiation with cisplatin, irinotecan, and bevacizumab. A pathologic complete response was seen in 4 of 33 patients (12%). Progression-free survival and overall survival were 14 and 30 months, respectively. Shows some promise in certain stages of cancer, (i.e. t3n1). Cetuximab / Panitumumab In esophagogastric cancer, variable rates of EGFR overexpression have been noted, ranging from 30% to 90%. phase III study. Patients with inoperable/metastatic esophageal, gastric, or GE junction cancer were randomized to receive EOC (epirubicin, oxaliplatin, capecitabine) with or without panitumumab. An early planned interim analysis showed that the panitumumab arm was statistically inferior after 553 (76%) patients were enrolled. Given the negative results of most trials, lack of efficacy with cetuximab, it is unlikely that anti-EGFR strategies will be further developed in the United States in unselected patients. Known Targets/New Agents HER2: Trastuzumab emtansine (T-DM1) International phase II/III trial in second-line advanced esophagogastric cancer will open randomizing between T-DM1 versus a taxane. Antiangiogenesis: Sorafenib Targets several kinases, including VEGFR1, VEGFR2, VEGFR3, Raf-1, Braf, and PDGFR1, for r use in renal cancer and hepatocellular. Hepatocyte growth factor/Mesenchymal epithelial transition factor (Hgf/Met) The cell surface receptor c-MET (mesenchymal–epithelial transition factor [MET]) and its ligand hepatocyte growth factor (HGF) are potential therapeutic targets in esophagogastric cancer. crizotinib is an orally bioavailable potent small-molecule inhibitor of MET. Rilotumumab is a human monoclonal antibody to HGF Heat shock protein 90 (Hsp90) is a chaperone protein that binds to the nucleotide-binding site and promotes the release of client proteins. Inhibition of Hsp90 is believed to cause these client proteins to adopt aberrant conformations, which are then targeted for ubiquitination and hence subsequent degradation. further understanding of potential synergy with radiation must be demonstrated before clinical trials ref- Theodore S. Hong, Jennifer Y. Wo, Eunice L. Kwak, Targeted Therapies with Chemoradiation in Esophageal Cancer: Development and Future Directions, Seminars in Radiation Oncology, Volume 23, Issue 1, January 2013, Pages 31-37, ISSN 1053-4296, 10.1016/j.semradonc.2012.09.004. (http://www.sciencedirect.com/science/article/pii/S1053429612000847)

Technical Considerations in Radiation Therapy for Gastroesophageal Junction Cancer

Incidence of distal and GOJ cancer have doubled over the past few years, mostly adenocarcinomas, and is associated with high mortality. chemoradiation therapy improves survival compared with surgery alone or with neoadjuvant chemotherapy followed by surgery, both in a neo and an adjuvant setting. This articles review technical considerations and data for radiation planning and field design for GE junction malignancies. Sim/CT Patient position is usually= arms placed overhead (ABC, T bar), with knee support underneath the legs for patient comfort. Patients are usually treated in the supine position, although some authors have advocated that patients with mid-esophageal tumor involvement should be simulated in the prone position to maximize distance between the target volumes and spinal cord. Motion of the thorax due to breathing can be monitored via 4D CT and gating, but the clinical benefit of respiratory motion is still not really understood. GTV Endoscopy reports as well as various imaging modalities, including barium swallow, CT, positron emission tomography (PET), and endoscopic ultrasonography (EUS), are useful to determine the gross tumor volume (GTV). PET has emerged as an important tool in staging esophageal and GE junction cancer patients, particularly in detecting occult stage IV disease. PET demonstrated improved accuracy compared with CT (82% vs 64%) for diagnosing patients with stage IV disease. EUS provides accuracy rates of 85%-90% for T stage and 75%-80% for N stage. CTV The extent of microscopic delineation of GOJ is a challenge due to the rich submucosal lymphatic network in both the oesophagus and stomach. A margin of 5 cm above and below the primary GTV is generally recommended to account for subclinical disease spread. Although not well defined, an approximate 1.5- to 2-cm radial margin expansion is recommended from the GTV to the CTV. PTV Intrafraction variations in target location, in large part due to organ motion during the respiratory cycle, or interfraction variability due to stomach filling can lead to variation in position of the CTV, thus PTV margin is added, In general, distal esophageal cancers appear to have greater respiratory motion than more proximal lesions, particularly in the cranial–caudal direction. RT adjuvant- post surgery, the recurrence rates are 30%-40% after R0 resection, thus giving emphasise towards additional adjuvant therapies. 3dCRT vs IMRT = CRT - improved dose conformality around target structures and normal-tissue sparing. IMRT- varying the dose intensity between each area of sub field, using inverse planning to provide steep dose gradients. 3d CRT- general approach is to use an initial anterior-posterior/posterior-anterior (AP/PA) approach with right anterior oblique/left posterior oblique fields to minimize dose to the heart/left ventricle, total dose for GE junction tumors ranges from 45 to 50.4 Gy. significant difference in mean heart dose (22.9 vs 28.2 Gy) and right coronary artery mean dose (23.8 vs 35.5 Gy) in favor of IMRT planning. This article also goes through ranges of OAR tol doses if you want to read more into it. Joseph M. Pepek, Christopher G. Willett, Brian G. Czito, Technical Considerations in Radiation Therapy for Gastroesophageal Junction Cancer, Seminars in Radiation Oncology, Volume 23, Issue 1, January 2013, Pages 51-59 this whole issue is devoted to Gastro-esophageal cancer if u want a look

Exploring the relationship between coping, social support and health-related quality of life for prostate cancer survivors: A review of the literature

The improved treatment of prostate cancer has lead to a decease in overall mortality however with more people living with the consequences of their treatment, there is more potential risk of late side effects, and for prostate cancer these inc chronic and enduring urinary, bowel, and sexual dysfunction for many years. These may all affect QoL. Past studies show prostate ca survivors have unmet needs, meaning many cope alone (studies cited in article) “need for informational support, particularly regarding the side-effects of the disease, associated treatments and on-going issues related to recurrence”. The addiction of social support may address the complex physical and psychological needs for men affected by PC. two dominant theoretical frameworks that link social support to improved physical and mental well-being: the Main Effects Model and the Stress Buffering Model . IN this metanalysis - searches were restricted to the search terms “prostate cancer”, “prostate carcinoma”, “health related quality of life”, “quality of life”, “social support”, “support groups” and “psycho-social”, “coping” and “adjustment”. The majority of the reviewed studies were prospective longitudinal and cross-sectional and therefore, there is limited evidence to identify the effect of social support on HRQoL at this time. reviewed data has identified that perceived social support, received social support and satisfaction with social support has been found to influence HRQoL for prostate cancer survivors. Some studies added support to the stress buffering model. existing evidence is largely restricted to the assessment of perceived social support. Perceived social support has been found to reflect more of personality disposition. Conclusion- more research required in coping and social support in QoL, adding multidimensional inventory not restricting to just one or two constructs. “Practically, this review has identified men who are highly distressed or who have inadequate support provisions are likely to benefit from social support intervention” Exploring the relationship between coping, social support and health-related quality of life for prostate cancer survivors: A review of the literature, European Journal of Oncology Nursing, Available online 31 May 2013

Energy management- a critical role in cancer induction

cancer induction- age-associated; even very high-risk “cancer genes” such as BRCA-1 take many years to produce tumors, which suggests induction is a concatenated multi-factorial process. identifying cells that become at risk or pose the greatest clinical threat, “cancer stem-cells (CSC's) and Cancer Initiating Cells (CIC's)” are described as originators and metastatic initiators respectively. Energy discussed i.e. Intuitively, the hallmark of increased motility and invasiveness in cancer cells must require more ATP but paradoxically many cancer cells use glycolysis rather than oxidative phosphorylation (oxphos) to generate it (the Warburg effect)- related to the mitochrondria, changes in signalling; mitochondrial suppression through reactive oxygen species and hypoxia- responsive genes such as HIF; metabolic competition decided by proliferative state (the “Crabtree effect”). The energy used in cell interactions and motility of cell organelles is also important, in what the authors call Fractal Entropic self sorting. AMP kinase (AMPK) also upregualted in cancers, suggesting metabolic pathways maybe linked to AMPK and energy metabolism, together with fact the AMPK is linked to mTOR. Authors link IL-3 as a growth factor- i.e. withdrawing IL3 causes immediate cessation of glycolysis but has no effect on ATP levels. Authors propose a model- To summarise, the model predicts the following: 1. The degree of “malignant” activity is proportional to the degree of structural fluidity (simplification of entropic energy dissipation). 2. Cancer cells will exhibit mixed metabolism with a bias towards glycolysis. 3. Cancer cells will be poorly distinguished from the normal population, but “onco-antigens” may arise depending on how the degradation re-assembles protein complexes. 4. Many, and often multiple, mutations will arise but will be biased towards the phenotype of the originating cell; and they will take time to create an effect since these are stochastic and dependent on fractal connectivity, which is inherently stable. 5. Targeting specific mutations may, or may not, work depending on where that mutation sits in the fractal interfacing. The overall direction of energy dissipation in cells is from release of energy “locked in” in high-energy metabolic substrates (eg. sugars) into coherent and balanced structure and activity. During this process, energy is released and dissipated (entropy) -cancer is an imbalance in this energy re-distribution. Ref- Energy management- a critical role in cancer induction. Critical reviews in oncology.hematlology. 2013.

Brachytherapy: Current Status and Future Strategies — Can High Dose Rate Replace Low Dose Rate and External Beam Radiotherapy?

Brachytherapy, results in rapid fall-off in dose and sparing of neighbouring organs, allows for much higher dose excalation as what can be acheiveed by EBRT (which is limited to OAR). Two types, low dose rate (LDR), involving the permanent implantation of radioactive seeds, and high dose rate (HDR). This study reviews the “current status of prostate brachytherapy, describe emerging trends and address the question of whether HDR can replace LDR and EBRT” LDR Started with I-125, and the development of TRUS guidance. Now standard treatment for men with low- and intermediate-risk disease prostate cancers. A multicentre clinical trial from the Radiation Therapy Oncology Group (RTOG 9805) reported a 92% biochemical disease-free survival after 8 years, with no deaths from disease. With good-quality implants, patients with low-risk disease can expect a long-term disease-free survival in excess of 90% after brachytherapy alone. However other studies do show much higher variation of OS and DFS, this maybe due to differing protocols (i.e. differing planning systems and patients treated with or without ADT). Brachy and EBRT is usally combined to give better dose escalation, but this is reported to increase the rate of grade 3 unrinenary toxicities. There is less knowledge about whether brachy monotherapy can be used in intermedicate risk patients, there is much more evidence regarding its use in higher risk patients. >high-grade prostate cancer managed with radiotherapy. Compared with treatment with EBRT alone, the addition of brachytherapy was associated with a 23% reduction in cause-specific mortality HDR Via temporarily implanted catheters via TRUS placement. “Images are then acquired with the catheters in place and transferred to a planning system”. “Anatomy-based inverse planning is used to optimise the dwell time at each position along the catheters to sculpt the resultant dose to achieve target coverage while limiting the dose to organs at risk”. HDR is most commonly used as a method of local dose escalation in combination with EBRT to treat patients with intermediate- and high-risk disease, with >85% DFS for patients with low/inter risk disease. There is now a trend of using fewer fractions, with several series reporting favourable results with the use of a single large HDR dose, esp for prostate which has lower a/b ratio. Morton et al (cited in article) reported no difference in biochemical control or toxicity between an HDR boost dose delivered as either two fractions of 10 Gy each or as a single dose of 15 Gy. Adding HDR to EBRT as a boost results in much higher DFS (Hoskins et al, cited in article). Use of HDR alone = Selected high-risk patients have also been treated with HDR monotherapy, with reported recurrence-free survival of 79–93%. The biggest challenge with HDR monotherapy is to define the optimum dose fractionation schedule. HDR v LDR HDR also has some cost advantages, as unlike LDR, the same radioactive source is used to treat many patients over several months. dose distribution is a more accurate due to the catheters afterloading and MRI/CT planning (thus seed placement each time is more accurate). Target coverage and normal tissue sparing is more consistently achieved with HDR than with LDR. However HDR delivers a large dose of radiation over several minutes, whereas with LDR implants, the radiation dose is delivered over several weeks or months. Prostate cancer seems to be particularly suited to radiation treatment delivered at a large dose per fraction. LDR brachytherapy, almost all patients experience significant obstructive and irritative urinary symptoms that last several months. This article does give good details into rationale regarding LDR/HDR in low or high risk patients. But does not pick a side when comparing HDR v LDR or if protocols locally can be changed to include brachy monothreapy. Morton & Hoskin 2013. Clinical Oncology.

A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial)

A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial) - Corrected Proof surgery remains best treatment option for early stage NSCLC. However there is still risk and local failure due to micrometastatic disease. Thus adding chemotherapy pre or post surgery may offer benefits. Based on other studies, this study hypothesis was adding neo-adj chemo will increase OS. open-label, 2 × 2 factorial randomised trial in patients with clinical Stage I (including T1N0) or II resectable NSCLC compared chemo regimes - 1 ) 2 cycles pre, then assess patient for repsonce then if good repsonse continue for 2 more cycles 2) pre cycles pre op, two cycles post op these two arms were then split into two hands 1) testing regime gemcitabine/cisplatin (GP), vs 2)paclitaxel/carboplatin (TC) end point were OS, DFS plus measure of QoL. All four groups seem to be split with equal variation across. results- overall, no diff between full neo adjvant and the pre and post chemo group. QoL slightly better in the neo adjuvant group. "The results of this randomised trial showed that the delivery of four cycles of preoperative chemotherapy in responders did not increase survival when compared with two preoperative plus two postoperative cycles in Stage I and II NSCLC. There was also no difference in survival between the two chemotherapy regimens, GP and TC" reasons cited for non results- inc stage 1 disease which there is little data to ponder as regards to adding chemo to surgery.Also many of the pre op arm were non responders thus did not recive all four cycles Study suggests clearer guidelines for the treatment of early stage NSCLC (i.e. adding chemo) " It has been shown that only a certain proportion of patients benefit from adjuvant cisplatin-based chemotherapy" EJC 2013