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01.08.2016
Treatment options for the various disease stages are given in Table 2, along with 5-year survival rates.
Only 40% to 60% of patients with esophageal cancer present with clinically localized disease.
Chemoradiation therapy as primary management of localized or locoregionally confined esophageal cancer has been shown to be superior to irradiation alone. For tumors of the intrathoracic esophagus (squamous cell carcinomas) and tumors with extensive Barrett esophagus (adenocarcinomas), it is often necessary to perform a total esophagectomy with cervical anastomosis to achieve a complete resection.
The resected esophagus may be replaced with a tubularized stomach in patients with tumors of the intrathoracic esophagus or with a colon interposition in patients with tumors involving the proximal stomach, because such involvement can make this organ unsuitable for esophageal reconstruction. The need for pyloric drainage (pyloroplasty) following esophagectomy is another area of debate.
Japanese series include mostly patients with squamous cell carcinomas of the intrathoracic esophagus, with 80% of the tumors located in the proximal and middle sections of the esophagus.
In a retrospective study, Akiyama found a 28% incidence of cervical node metastases in patients with squamous cell carcinomas located in the middle and distal portions of the esophagus, as opposed to 46% in those with tumors of the proximal third. In a study of 1,000 patients with esophagogastric junction adenocarcinomas, the tumors were classified according to the location of the center of the tumor mass in adenocarcinomas of the distal esophagus, cardia, and subcardia. The frequency of metastatic disease as the cause of death in patients with esophageal cancer has resulted in exploration of the early application of systemic therapy for esophageal cancer. However, the Medical Research Council evaluated 802 patients with resectable esophageal cancer in a similar study.
Given the uncertainty about the efficacy of preoperative chemotherapy and chemoradiation therapy, some investigators have administered preoperative chemotherapy, followed by chemoradiation therapy, then surgery. Because the most common source of treatment failure in patients with esophageal cancer who have undergone surgical resection is distant metastatic disease, postoperative chemotherapy has also undergone limited investigation. Although radiotherapy alone is inferior to chemoradiation therapy in the primary management of locoregionally confined esophageal cancer, it may offer palliation to patients with advanced local disease who are too frail to be managed with chemotherapy. The superiority of preoperative chemoradiation therapy over surgery alone in esophageal adenocarcinoma has been investigated in several prospective trials. A meta-analysis of randomized trials comparing neoadjuvant chemoradiation therapy followed by surgery with surgery alone found that neoadjuvant concurrent chemoradiation therapy improved 3-year survival (odds ratio, 0.66) compared with surgery alone, with a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation.
A phase II trial from Memorial Sloan Kettering Cancer Center combined cisplatin and irinotecan with 50.4 Gy of radiation therapy followed by surgery. Several schedules of oxaliplatin (Eloxatin) and 5-FU concurrently with radiation have been investigated. Adding anti-EGFR (epidermal growth factor receptor) therapy with cetuximab or panitumumab to neoadjuvant chemoradiation appears to be feasible in small phase I and II studies, but it has not clearly been shown to improve pathologic complete response rates, and the large randomized trial known as REAL-3 failed to show any benefit from perioperative chemotherapy with panitumumab. The EGFR antagonist cetuximab has been demonstrated to have radiation sensitization effects in squamous cell carcinomas of the head and neck. Bedenne et al presented results of a randomized trial of preoperative chemoradiation therapy vs chemoradiation therapy alone, in which there was no difference in median or 2-year overall survival rates.
Newer forms of radiation therapy, such as proton beam therapy, are being studied in combination with chemotherapy.
Most of the trials demonstrating the efficacy of chemoradiation therapy have had a high proportion of patients with squamous cell cancers. The literature also supports offering primary surgery, preoperative chemoradiation therapy, or primary chemoradiation therapy with surgical salvage if necessary to patients with adenocarcinoma.
Ajani et al reported on a series of 43 patients who received 12 weeks of cisplatin and irinotecan followed by weekly paclitaxel with infusional 5-FU and concurrent radiation therapy (4,500 cGy) and then esophagectomy. After definitive therapy for esophageal cancer, the optimal surveillance strategy for recurrent or second primary disease is uncertain.
Esophagectomy following induction chemotherapy and chemoradiation therapy for squamous cell carcinoma.
At ASCO 2013, Alberts et al reported on North Central Cancer Treatment Group N0849, which examines the use of extended neoadjuvant chemotherapy, since delivery of post-chemotherapy may be difficult. The incidence of residual disease in patients who have a complete clinical response to chemoradiation therapy is 40% to 50%, and those patients who have a pathologic complete response to chemoradiation therapy have the best survival rates with surgery. The goal of esophageal cancer treatment is generally palliative for patients with bulky or extensive retroperitoneal lymph nodes or distant metastatic disease. Porfimer (Photofrin) and an argon-pumped dye laser can provide effective palliation of dysphagia in patients with esophageal cancer. A review of 119 patients treated with endoluminal palliation reported a significant improvement in dysphagia scores and an increased ability to relieve stenosis caused by tumor when PDT was used in conjunction with laser therapy and irradiation. Other approaches include EBRT with or without an intracavitary brachytherapy boost, simple dilatation, placement of stents, and laser recannulization of the esophageal lumen. Palliative resection for esophageal cancer is rarely warranted, although it does provide relief from dysphagia in some patients.
At this time, most studies in esophageal and GE junction cancers categorize them by histology: gastric and GE junction adenocarcinomas, or esophageal squamous cell carcinomas.
Phase I and II studies have demonstrated moderate response rates to chemotherapy in esophageal cancer. Although chemotherapy alone may produce an occasional long-term remission, there is no standard regimen for patients with metastatic cancer. Although the regimen has been fairly well tolerated, infusional 5-FU has rendered the combination unpopular in other countries.
With the advent of many new chemotherapeutic agents (the taxoids, paclitaxel and docetaxel [Taxotere], irinotecan, and gemcitabine [Gemzar]) with varying mechanisms of activity, further studies have been conducted, and each of these drugs has demonstrated activity, with responses achieved in approximately 15% to 30% of patients.
Because of the toxic and logistic difficulties of using cisplatin, carboplatin has become a popular chemotherapeutic drug. The combination of docetaxel, cisplatin, and infusional 5-FU (DCF) has been approved by the US Food and Drug Administration for the treatment of metastatic gastric and GE junction adenocarcinomas.
Another response to the toxicity of the DCF regimen has been the elimination of the 5-FU, and exploration of cisplatin and docetaxel alone or substitution of oxaliplatin for cisplatin.
The antimetabolite gemcitabine has also been evaluated in combination with cisplatin in esophageal cancer.
Oxaliplatin may also have a role in the treatment of esophageal cancer, both as a radiosensitizer and an agent in advanced disease. The primary toxicity of these regimens is severe neutropenia, occurring in about 40% to 70% of patients. With improving toxicity profiles and modest improvements in therapeutic outcomes, second-line therapy for advanced esophageal cancer is also increasingly being explored.
Oral tyrosine kinase inhibitors of the EGFR have also been investigated in esophageal cancer. The other class of agents that target the EGFR pathway, monoclonal antibodies such as cetuximab, has provided mixed results in patients with esophageal cancer. The SWOG studied cetuximab as a single agent as second-line therapy for metastatic esophageal adenocarcinoma. The role of the vascular endothelial growth factor (VEGF) pathway in esophageal cancer also remains unclear.
In addition to the EGFR and VEGF antagonists, it is anticipated that other targeted therapies, such as MEK and met inhibitors, will be evaluated in this disease.
Cervical Cancer ? Only 3,700 deaths predicted in 2006? Caused by Human Papilloma Virus (HPV) • Persistent infections can cause dysplasia, and cause cancer over 10-15 years • HPV 16 and 18 account for 70% of cases ? Primary Prevention • HPV vaccination (covers just HPV 16 and 18) – 3 shot series for girls 11-25.
What the Guidelines Say ? Cervical Cancer (ACS, ACOG, USPTF) • Pap within 3 years of first sexual activity or at age 21• Stop at 65 in low risk women and after hysterectomy for benign disease • Frequency of 1-3 years according to risk ? Smoker, Prior Abnormal Pap Tests, Multiple Partners • HPV testing – unclear if health outcomes will be better. Things to Remember about Colonoscopy ? Expensive, requires bowel prep, usually involves sedation and missed work. Prostate Cancer ? #3 cause of cancer death in US men (was #2 until recently) ? Incidence increases • After age 50 • After age 40 in African American Men ? Modifiable risk factors: • Obesity? Informed Decision Making ? Consider life expectancy before ordering? Consider consequences abnormal tests? Discuss with patients and listen to their concerns before ordering! What the Guidelines Say ? Lung Cancer (ACS, ALA, USPTF) • Screening is not currently recommended• Smoking cessation!• Smoking prevention! The anterior fibromuscular stroma also appears as an area with low signal intensity on T2-wi [1]. 2 clicks for more privacy: On the first click the button will be activated and you can then share the poster with a second click.
This entry is part 17 of 25 in the series Our milestonesOne hundred years ago a great conflict began that would change the world forever. In July 1917, troops based in Ypres, Belgium, reported a shimmering cloud around their feet and a strange peppery smell in the air. They’d been poisoned by mustard gas – one of the most deadly chemical weapons deployed in battle. Towards the end of the Great War, this gas had not only killed and crippled but instilled terror across the battlefield.
Mustard gas was one of a number of weaponised poison gases developed by Fritz Haber, a Professor at the prestigious University of Karlsruhe.
But Haber’s role in chemical weapons’ development means his legacy will always have its dark side.
Two decades later, with World War II looming, researchers on the side of the Allied Forces feared a repeat of the mustard gas attacks of the Great War. Two doctors at Yale University, Louis Goodman and Alfred Gilman, delved into the medical records of soldiers affected by mustard gas, and noticed that many of them had a surprisingly low number of immune cells in their blood – cells that, if mutated, can go on to develop into leukaemia and lymphoma. Goodman and Gilman hypothesised that if mustard gas could destroy normal white blood cells, it seemed likely that it could also destroy cancerous ones. After successful animal trials, Goodman and Gilman looked for a human volunteer with white blood cell cancer to test mustard gas as a cancer therapy.
He received a number of treatments with substance X and with each one he became a little better.
Back in the UK and after WWII, another brilliant chemist, Professor Alexander Haddow, became Director of the Chester Beatty Research Institute – an Institute funded by one of the founding charities that merged to form Cancer Research UK.
All he needed to make a breakthrough in cancer treatment was a lead – an effective molecule to start from. In 1948, Haddow published a ground-breaking piece of research in the journal Nature, showing exactly which bits of the nitrogen mustard molecule were needed to kill cancer cells.
This was an important finding, showing that the molecule needed both chlorine atoms to work. He continued his research, showing how these chemicals actually worked – it was by somehow linking together other molecules inside the cancer cell, ultimately leading the cell on a suicidal path. And so mustard gas went from the very real battleground of the WWI trenches into the frontline of cancer treatment. But Haddow’s subsequent work launched the start of a new era of cancer treatment – chemotherapy. The chemical structure Haddow published is only a few atoms away from the structure of the drug chlorambucil, which is still used to treat a type of leukaemia called chronic lymphocytic leukaemia and another blood cancer called non-Hodgkin lymphoma (NHL). Haddow’s research led to the development of more chemotherapy treatments that have completely changed the outlook for other types of cancer. So we have developed, and will continue to develop, more and more targeted treatments designed to pick out specific cancer targets – like a sniper selecting precisely who to ‘take out’. But for now there’s still a place for chemotherapy – one of the first chemical weapons in our ever-growing arsenal against cancer. Text from Cancer Research UK Science blog by Cancer Research UK, is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Cancer Research UK is a registered charity in England and Wales (1089464), Scotland (SC041666) and the Isle of Man (1103).
The Cancer Council National GP Portal is a directory site that points to information on other sites, so there is no search function.
The National Comprehensive Cancer Network guidelines state that patients with clinically localized disease may be treated with resection or chemotherapy plus irradiation (Tables 3 and 4). A series of randomized trials have demonstrated that adjuvant postoperative chemoradiation therapy does not offer a survival advantage to patients with esophageal cancer, save perhaps for those affected at the GE junction, as demonstrated in part in INT-0116. Preoperative medical evaluation helps determine the patient’s risk of postoperative complications and mortality.
The extent of resection depends on the location of the primary tumor, histology of the tumor, and nature of the procedure (palliative vs curative). For distal lesions of the abdominal esophagus (adenocarcinomas) and cardia, it is often possible to perform an intrathoracic esophageal anastomosis, although many surgeons would prefer to perform a total esophagectomy. The esophageal replacement is usually brought up through the posterior mediastinum, although the retrosternal route is often used in palliative procedures.


A meta-analysis of nine randomized trials that included 553 patients showed a trend favoring pyloric drainage in improving gastric emptying and nutritional status, whereas bile reflux was better in the nondrainage group.
Considerable controversy exists regarding the need for radical lymphadenectomy in esophageal disease. Americans report combined series, with at least 40% to 50% of patients with adenocarcinomas of the distal esophagus. Overall survival at 5 years was significantly better in patients who underwent extended lymphadenectomy (three fields) than in those who had conventional lymphadenectomy (two fields); this finding was true in patients with negative nodes (84% and 55%, respectively) and in those with positive nodes (43% and 28%, respectively). The tumors located in the cardia and subcardia regions spread primarily to the paragastric and left gastric vessel nodes and did not benefit from extended esophagectomy. The first of the two large studies was RTOG (Radiation Therapy Oncology Group) trial 8911 (USA Intergroup 113).
The true utility of this approach will need to be defined by randomized studies (that carefully match for histology, anatomic location, radiation techniques, and chemotherapy), but clearly it is feasible, without a significant increase in toxicity or operative morbidity. The Japanese Cooperative Oncology Group has compared preoperative and postoperative chemotherapy in 330 patients with stage II or III esophageal squamous cell carcinomas. Preoperative radiotherapy has been shown to be of little value in converting unresectable cancers into resectable ones or in improving survival.
Postoperative radiotherapy (usually to 50 or 60 Gy) can decrease locoregional failure following curative resection, but it has no effect on survival. Intraluminal isotope radiotherapy (intracavitary brachytherapy) allows high doses of radiation to be delivered to a small volume of tissue. Initial trials of preoperative chemoradiation therapy reported unacceptably high operative mortality (approximately 26%). The first trial (Walsh et al: N Engl J Med 1996), in Ireland, included 113 patients with adenocarcinoma of the esophagus. Most of the 363 patients enrolled in this study, all of whom had potentially resectable disease at the time of enrollment, had adenocarcinoma (75% vs 23% squamous cell carcinoma).
None of the studies have been large enough or the results conclusive enough to result in the widespread adoption of oxaliplatin in place of carboplatin or cisplatin with radiation in esophageal cancer. Patients with locally advanced esophageal cancer (T1-4 N0-1 M0) may be cured with definitive chemoradiation therapy.
A randomized intergroup trial was designed to investigate the role of high-dose irradiation in conjunction with systemic therapy. Chemoradiation therapy has thus become standard treatment of locoregionally confined squamous cell cancer of the esophagus.
Only modest benefits have been found with preoperative chemoradiation therapy to date, with systemic failure continuing to be an important problem.
Therapy was well tolerated, with no deaths from chemotherapy or chemoradiation therapy, and an operative mortality rate of 5%.
However, there was no significant difference in operative morbidity or mortality between the two approaches at this high-volume referral center. Because of the primary threat to survival, CT scans are often ordered at 6- to 12-month intervals.
Controversy exists regarding the need for esophagectomy following chemoradiation therapy in patients with squamous cell carcinoma, which tends to respond well to chemoradiation.
Pathologic complete response was higher (15.6% vs 2%) and 3-year survival was trending toward improvement (47% vs 28%) in patients who received preoperative chemoradiotherapy.
Since esophageal cancer is being diagnosed in more patients at older ages, research is ongoing as how best to treat elderly patients. Therapeutic approaches should temper treatment-related morbidity with the overall dismal outlook. The data are from studies that include a substantial proportion of patients with metastatic gastric cancer, as opposed to esophageal or GE junction adenocarcinomas.
Patients with advanced disease should be encouraged to participate in well-designed trials exploring novel agents and chemotherapy combinations. However, in the remainder of the world, there is no regimen that is considered to be the standard treatment of metastatic esophageal cancer. Several phase III studies have been performed and consistently demonstrated objective responses in about 40% of patients, with a median survival of 9 months and a 1-year survival of 36% to 40%. The results available to date suggest promising activity, with response rates often around 50% in phase II studies. They were reported to produce objective responses in 43% of 51 patients, including two complete responses, and 43% of patients were alive 1 year after initiation of therapy (Table 5). Thirty-eight percent of the 51 treated patients had objective responses, with a median survival of 8 months and a 1-year survival rate of 26%.
Severe diarrhea, nausea, and vomiting occur in approximately 10% to 15% of patients in many studies.
However, only three partial responses (13%) and eight patients with stable disease were noted, with a resultant median survival of 26 weeks. Gefitinib (Iressa), at a daily dose of 500 mg, as second-line therapy in patients with esophageal adenocarcinomas was evaluated by Ferry et al.
Each arm included about 80 patients; the response rates were 58%, 38%, and 51%, respectively, and median survivals were 8 to 10 months. Of the 55 eligible and evaluable patients, only one (2%) had a partial response, and six (11%) had stable disease.
A phase II study of a modified DCF with bevacizumab demonstrated a response rate of 67% and median survival of 16.8 months in 44 patients with GE cancer, which is superior to DCF alone, suggesting a potential utility of bevacizumab in this disease. Such avenues of exploration, in addition to early diagnosis of and therapy for early-stage disease, are the most likely path toward significant improvements in therapy for esophageal cancer.
If you interesting in "Cervical Cancer Prevention· Screening· Evaluation · Treatment" powerpoint themes, you can download to use this powerpoint template for your own presentation template. World War I, also known as the Great War, would leave 17 million people dead or missing in action. Within 24 hours they started to itch uncontrollably and developed horrific blisters and sores. Haber was a brilliant chemist, who invented a process for the industrial scale production of ammonia-based fertiliser.
And his colleagues would go on to make other deadly gases – World War I is known to some as the chemists’ war.
At 10am on the 27th of August 1942 he was given the first injection of what they called “synthetic lymphocidal chemical”. Perhaps more importantly, he also found out how to make the chemical less toxic, but with more potent cancer-killing activity.
Then in experiments akin to tinkering with Lego, he altered bits of the molecule, replacing them with different ‘bricks’. Other researchers then went on to show that these linked molecules were in fact strands of DNA. Survival from NHL has nearly trebled since the early 1970s and now over 60 per cent of people survive for at least 10 years, thanks in part to this drug.
And anyone who’s been through it knows that, despite decades of evolution away from the trenches, chemotherapy is still, for many, a very difficult and unpleasant experience. We also highlight other relevant material, debunk myths and media scares, and provide links to other helpful resources.
Visitors will find the latest news and research, and a comprehensive suite of resources to assist GPs and their patients in the process of cancer prevention, diagnosis and treatment. The overall 5-year survival rates for either surgery alone or combined chemotherapy and irradiation appear equivalent. Adequate patient selection, tumor staging, and treatment standardization will be required before the optimal therapeutic modalities in these patients will be determined. In addition to the staging and nutritional status, it should include an evaluation of the pulmonary, cardiac, renal, and hepatic functions. A retrospective study has reported that superficial mucosal lesions (T1a) may be treated via endoscopic mucosal resection, but those patients with submucosal invasion (T1b) require esophagectomy. Clearly, patients with distant metastases, evidence of nodal metastases in more than one nodal basin, or tumor extension outside the esophagus (airway, mediastinum, vocal cord paralysis) are candidates for palliative therapy.
To date, two randomized studies have compared transhiatal esophagectomy (without thoracotomy) with the Ivor-Lewis (transthoracic) esophagectomy (with thoracotomy). The gastric emptying time evaluated by scintigraphy was twice as long in the nondrainage group as in the pyloric drainage groups. Skinner and DeMeester favor en bloc esophagectomy with radical (mediastinal and abdominal) lymphadenectomy, based on 5-year survival rates of 40% to 50% in patients with stage II disease, as compared with rates of 14% to 22% in historical controls. Extended lymphadenectomy was not associated with a survival advantage in patients with tumors in the distal third of the esophagus.
Kato et al have studied the use of sentinel node mapping to improve the sensitivity of lymphadenectomy. A total of 440 patients were treated with surgical resection alone or preceded by three cycles of cisplatin and fluorouracil (5-FU).
Microscopically complete resection was performed more frequently in patients receiving chemotherapy, with no difference found in postoperative complications or mortality. Interestingly, these reports have also demonstrated that most patients had significant improvement or resolution of dysphagia with the induction chemotherapy alone.
Retrospective studies suggest that a brachytherapy boost may result in improved rates of local tumor control and survival over external beam radiation therapy (EBRT) alone.
Subsequent trials reported operative mortality of 4% to 11%, median survival as long as 29 months, and 5-year survival rates as high as 34%.
These patients were randomized to receive either preoperative chemoradiation therapy (two courses of 5-FU and cisplatin given concurrently with 40 Gy of radiotherapy in 15 fractions) or surgery alone.
A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy.
Randomized trials have demonstrated a survival advantage for chemoradiation therapy over radiotherapy alone in the treatment of esophageal cancer.
Kachnic et al reported a subsequent quality-of-life analysis that confirmed lower mean quality of life in the high-dose radiotherapy arm, providing further data that 50.4 Gy is the recommended dose of radiation therapy in the definitive setting. It is essential that chemotherapy be given concurrently with irradiation when this approach is chosen as primary treatment for esophageal cancer.
The 24-month overall survival rate was similar between those treated with cetuximab (44%) and those not (42%), as was cCR rates (56% vs 59%). Thus, sequential therapy with chemotherapy followed by chemoradiation therapy has been explored. Cisplatin and irinotecan induced responses in 37% of patients, and 91% of patients underwent complete resection. Nonetheless, this approach cannot be recommended for use outside the context of a clinical trial. Although previously described studies randomized patients to receive surgery with or without preoperative chemoradiation therapy, Stahl et al randomized patients to receive chemoradiation therapy with or without surgery. Retrospective studies from Nallapareddy et al have found chemoradiaton therapy is tolerable in elderly patients, whereas Rice et al have found a trimodality approach of chemoradiation therapy followed by surgery is also tolerable in the elderly. Most data relating to the treatment of unresectable and metastatic esophageal cancer are often derived from clinical trials in which patients with esophageal and gastric and gastroesophageal carcinomas are enrolled.
Difficulties in determining optimal therapy for this disease include the possible differences between esophageal squamous cell cancers and adenocarcinomas.
The main severe toxicities of this regimen are neutropenia, in about one-third of patients (32% to 36%), lethargy (18%), and nausea and vomiting (11% to 17%). Responses were noted in half of the 40 patients, with a median survival of 11 months and a 1-year survival of 46%.
Tebbutt et al performed a randomized phase II study in 106 patients with advanced esophagogastric cancers. This study was conducted in the Netherlands, and the tolerability and efficacy of this regimen in American patients remain to be determined. As expected, severe neutropenia was the dominant toxicity (88%, including nine episodes of febrile neutropenia), with severe anorexia, fatigue, and anemia also reported. Although these studies suggest the feasibility of second-line cytotoxic chemotherapy in esophageal cancer, the significant toxicity and limited objective response rate warrant its use only with caution and preferably on a clinical study. It produced partial responses in 11% of 27 patients, and an additional seven patients had stable disease. Each arm surpassed the prespecified endpoint, suggesting enough promise to further explore in phase III studies. The median progression-free survival was 1.8 months, the median survival was 4 months, and the 6-month survival rate was 36%.


In addition, a study of sorafenib, 400 mg twice daily, demonstrated one complete response and one prolonged stable disease in 20 patients. For viewing only, you can play with our flash based presentation viewer instead of downloading the ppt file. Stuck in the squalid conditions of the trenches, it was a living hell for those on the front line.
This brilliant discovery, known as the Haber process, played a huge role in avoiding worldwide famines and now feeds about a third of the world’s population. Replacing certain bits, in particular either of two chlorine atoms, rendered the molecule useless and it no longer blocked tumour growth in his rats. Through this molecular puzzle Haddow worked out which pieces were needed to make a treatment that would benefit cancer patients across the globe. This triggered the cell’s self-destruct mechanism – causing the cell to shut down and break apart, destroying it. Although it worked initially, giving him an immensely important extra few months with less pain and greater comfort, he lost his life six months after his experimental treatment was started. And in fact, nitrogen mustard derived chemotherapy is still used to treat some cancers today.
And work continues on these sorts of treatments to make them kinder, with fewer side effects. Patients with disease limited to the esophagus and no evidence of nodal metastases (stages I and IIA) may be treated with esophagectomy, although these patients can also be considered for definitive treatment with chemoradiation therapy. These studies failed to show differences between the two procedures with regard to operative morbidity and mortality. The patients who received preoperative chemotherapy demonstrated a significant improvement in progression-free survival (2.9 years vs 2 years). Because of the 12% incidence of fistula formation, the investigators (Gaspar et al: Cancer J 2001) urged caution in the routine application of brachytherapy as part of a definitive treatment plan.
In general, 25% to 30% of patients have no residual tumor in the resected specimen, and this group tends to have a higher survival rate than those who have a residual tumor discovered by the pathologist.
Median survival was statistically superior in the combined-modality arm compared with the surgery-alone arm (16 months vs 11 months).
Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. In an RTOG randomized trial involving 129 patients with esophageal cancer, 80% of whom had squamous cell cancers, irradiation (50 Gy) with concurrent cisplatin and 5-FU provided a significant survival advantage (27% vs 0% at 5 years) and improved local tumor control over radiation therapy alone (64 Gy). Overall, the preoperative therapy was fairly well tolerated, and a pathologic compete response was found in 27% of patients.
Pathologic complete responses occurred in 26% of patients, and some tumor shrinkage was noted in 63% of patients. However, a retrospective evaluation of patients with esophageal adenocarcinoma who were treated with trimodality therapy including chemotherapy, radiation, and surgery at the MD Anderson Cancer Center from 2000 to 2010 suggested that anastomotic recurrence alone, without distant metastatic disease, is an infrequent event, occurring in 5% of patients, compared with 36% of patients who had anastomotic recurrence with distant metastatic disease. Also, all 172 patients in the study underwent initial induction chemotherapy (bolus 5-FU, leucovorin, etoposide, and cisplatin for three cycles).
Close monitoring for toxicities such as dehydration, nutritional concerns, anemia, and postoperative arrhythmia was recommended in these two studies. Similarly, patients in such studies may have either squamous cell carcinomas or adenocarcinomas.
Moreover, most of the available data regarding the treatment of metastatic esophageal cancer are derived from studies in which most patients had gastric cancer or from small phase II studies.
The REAL-2 study evaluated 1,002 patients (60% esophageal or GE junction cancer) with advanced esophagogastric cancers. A Korean phase II study did not confirm these results but did suggest the combination was active, with a response rate of 31% of 32 patients, and a median survival of 9.6 months. Objective responses were reported in 45% of patients, with a median survival of 9 months and 1-year and 2-year survival rates of 43% and 17%, respectively.
Both of these combinations were well tolerated, with the primary toxicity of myelosuppression. The regimen was reported as well tolerated, with about one-third of patients experiencing grade 3 or 4 neutropenia. The median survival rate was 7.1 months, the 1-year survival rate was 31%, and the 2-year survival rate was 11%. In patients with esophageal cancer that had previously been treated with platinum-based chemotherapy, Janmaat et al treated 37 patients with the same regimen.
Again, however, the number of patients treated was too low to consider any of the regimens to be a standard at this time. The authors concluded that although the drug was well tolerated as single-agent therapy, it did not meet its primary endpoint and so could not be recommended as second-line therapy in esophageal cancer. Taken together, these data suggest that inhibiting the VEGF pathway may improve outcomes in metastatic disease, and further investigation is ongoing.
And it’s largely responsible for the fact that 96 per cent of men with testicular cancer now survive the disease long term. Multiple retrospective studies in the United States and Europe document that short-term and even long-term outcomes are superior when esophageal resection is performed at high-volume centers (those performing approximately 8 to 12 procedures per year). In a randomized trial of 220 patients treated with either an extended transthoracic esophagectomy or limited transhiatal esophageal resection, no significant overall survival benefit was found for either approach, although extended transthoracic esophagectomy showed a trend toward an improvement in 5-year survival. With a median follow-up of 6 years, the updated results of this study continued to demonstrate a significant difference in overall survival at 5 years: 23% for patients who received preoperative chemotherapy vs 17% for patients treated with surgery alone—and this benefit was present in both histologies. Thus, the investigators determined that preoperative therapy would be the new standard therapy.
Rates of 3-year survival again statistically favored the combined-modality arm (32% vs 6%). There was no difference in postoperative complications or in-hospital mortality between the two arms. Median overall survival was 49.4 months in the chemoradiotherapy–surgery group versus 24 months in the surgery group. Cisplatin, docetaxel, and cetuximab were combined with radiation therapy by Ruhstaller et al prior to surgery, and this was found to be tolerable, with a complete or near complete pathologic regression in 68% of the patients. This trial was stopped after an interim analysis revealed no statistically significant difference in survival between the two groups.
Of the 21 patients in arm A, 2 did not proceed to chemoradiation and 2 died before proceeding to surgery. However, although subset analysis of data suggests a similar survival outcome in both histologic subsets, it is possible that there is a difference in response rates, by histology. The median survival of patients treated on this study was 7.3 months, and the 1-year survival rate was 20%.
In this setting, a response rate of 35% was reported, with a median survival of 7.4 months. They reported a confirmed response in only one patient and stable disease in another 10, although 18% of patients were free of disease progression at 6 months, suggesting that some patients indeed experience disease control and benefit from this therapy. Moreover, of the five patients who crossed over to second-line cetuximab, two had partial responses (one with single-agent therapy), and one had stable disease. Both cetuximab and panitumumab have been evaluated in large randomized phase III studies in patients with advanced or metastatic esophagogastric adenocarcinoma in the first-line setting. The discordant results represented in these studies, between histologies and drugs, may reflect the differing biologies of esophageal adenocarcinomas and squamous cell carcinomas. Still unknown if this translates into a true mortality benefit, but prostate cancer mortality is declining nationally.
Regionalization of surgical care of high-risk esophageal cancer patients may be even more beneficial.
Over the past 5 years, successful attempts have been made to use minimally invasive approaches to esophageal cancer with thoracoscopy and laparoscopy. The MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) study, which evaluated preoperative and postoperative chemotherapy with epirubicin, cisplatin, and infusional 5-FU in patients with GE cancer (about 25% had esophageal or GE junction tumors), also demonstrated a statistically significant improvement in survival with perioperative chemotherapy, with a hazard ratio [HR] of 0.75, suggesting a 25% increase in the likelihood of survival.
However, the fact that preoperative chemotherapy was superior to postoperative chemotherapy does not necessarily mean that there is no benefit to postoperative chemotherapy. Although toxicity was not severe, the short survival duration in the surgery control arm has minimized the impact of these results in the United States.
The FOLFOX (oxaliplatin, leucovorin, 5-FU) schedule concurrent with radiation has also been studied. In addition, Li et al reported on a small series of patients who received cisplatin, paclitaxel, and radiation therapy with erlotinib, 150 mg daily.
The authors concluded that higher-dose radiation therapy did not offer any survival benefit over the 50.4-Gy dose. The patients who had a pathologic response to therapy had significantly better outcomes than the rest of the study population. These findings suggest that surveillance for recurrent or metastatic disease that is amenable to treatment may focus on the history and physical examination, with radiographic imaging primarily during the first 3 years, and then with decreasing intensity. In this study, the outcomes were similar in the resultant treatment groups, with median survivals of about 10 months and 1-year survivals between 39% and 45%. However, the heterogeneity of the patient population makes the efficacy of the therapy somewhat difficult to assess. Although differences in patient populations were noted, these results are similar to those of other reported combinations. However, Radovich et al reported only one response in 23 patients treated with erlotinib (Tarceva; 150 mg daily). However, given the sample size, and the unblinded nature of the study with crossover, caution must be exercised when interpreting these results. IV-injected contrast agent reaches to the tissue microvasculature and extravasate within seconds to the extravascular extracellular space. A recent randomized trial from the Netherlands comparing minimally invasive versus open esophagectomy has shown decreased pulmonary morbidity and reduced blood loss in the minimally invasive group. Only about 40% of patients actually completed both preoperative and postoperative chemotherapy, but overall, this suggests that chemotherapy has benefit as preoperative therapy in esophageal cancer. Moreover, the role of adjuvant chemotherapy alone in esophageal adenocarcinomas is uncertain.
These data were confirmed in a similar study by the Eastern Cooperative Oncology Group using mitomycin-C rather than cisplatin with infusional 5-FU. However, systemic recurrences remained a prominent cause of failure, with five patients experiencing recurrence first in the brain and an additional five patients, in the liver. After a 6-year median follow-up, the local progression-free survival favored the group that underwent surgery (64% vs 41%).
The toxicities were as expected, including rash, diarrhea, vomiting, and elevation in transaminase levels.
Indeed, the outcomes were worse in the experimental arms of both studies, perhaps because of the increased toxicity, including diarrhea and dermatologic reactions, engendered by the additional drugs. Retrospective studies suggest that the rate of positive margins and lymph node harvest are comparable between minimally invasive and open approaches, although randomized data are not yet available for comparing the endpoints of local recurrence, disease-free survival, and overall survival. The reasons for the differences in the outcomes are unclear but may be related to the chemotherapy regimen and schedule employed in the Intergroup study, patient population, or study design. The study included 267 patients, of which 86% had squamous histology and 52% had stage III disease. However, the treatment-related mortality was higher in those patients who underwent surgery (13% vs 4%), and so overall survival was statistically equivalent (at 3 years, 31% vs 24%).
As with lung and colon cancers, the optimal population for treatment with these targeted agents remains to be defined. As a result, the role of neoadjuvant chemotherapy remains in question but is promising, especially with the potentially more efficacious, newer-generation chemotherapy agents.
Since induction chemotherapy was used in all patients, these results should not be extrapolated to indicate the value of esophagectomy following chemoradiotherapy alone. After initial uptake, three types of time-intensity curves can be identify, persistent increase (type 1), plateau (type 2) and decline after initial upslope (type 3).



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Comments to “Prostate cancer treatment guidelines 2014 bathrooms”

  1. FREEBOY:
    BPH, and part of a growing £396 date of blood.
  2. NOD32:
    The prostate makes the urethra.
  3. Gunel22:
    Cancer is confirmed by biopsy (removal of pieces of the prostate to look the immediate post operative outcome well as to treat.
  4. Rocco_Barocco:
    Protein made by the prostate that is in the with.