Its also important to follow recommended screening guidelines, which can help detect certain cancers early. Tumours were located in the distal extremities in 2,424 cases (49.0%), in the proximal upper extremity in 461 cases (9.3%), in the proximal lower extremity in 1,800 cases (36.4%) and in the trunk in 257 cases (5.2%). Then researchers examined which factors had the greatest impact on the survival of patients for 12 years. So, lets consider the main factors that affect survival and recovery in sarcoma. Grimer estimated that for every centimetre increase in tumour size at the time of diagnosis, there is a 35% reduction in overall survival for STS.19 As expected, the presence of metastases at diagnosis reduced survival and the proportion of cases with metastasis present increased almost linearly with increasing tumour size (Fig2).19 Histological tumour grade has been shown to be the most reliable independent prognostic factor at diagnosis for mid to long-term survival14,23 and there was a similar magnitude of effect in our data. Metastatic means the sarcoma has spread to parts of the body far away from where the sarcoma started. The causes of death were classified into: primary cancer (local recurrence, metastatic disease), treatment related (either postoperative or following adjuvant chemo/radiotherapy), other unrelated causes and unknown causes. Of these, 595 (12%) died within 1 year of diagnosis. Soft tissue sarcoma patients who survived over one year reported a longer duration of symptoms preceding diagnosis than those who died (median: 26 vs 20 weeks, p<0.001). After a cancer diagnosis, staging provides important informationabout the extent of cancer in the body and anticipated response to treatment. The fact that breast lumps average 2.1 cm at diagnosis indicates that the breast clearly has a greater awareness in people's minds than the rest of the body. for every 1 cm increase in size, the risk of dying is increased by a factor of 1.059). The mean size of sarcomas presenting to our unit was 10.7 cm at the time of diagnosis. Who Gets Ewing Sarcoma? Bone sarcomas averaged 11.3 cm with little variation by age or diagnosis, whilst subcutaneous soft tissue sarcomas averaged 10 cm. Histological rank is the decisive factor of the chances of recovery from sarcoma. Incidence of metastases at presentation split by size categories (soft tissue sarcoma data). This is possibly not surprising as bone tumours virtually all originate within the bone and will grow to a certain size before they break through the bone and start elevating the periosteum. The distant category is equivalent to stage 4 metastatic cancer. 1). In general, the 5-year survival rate of patients with localized disease is 83%, in patients with regional disease, 5-year survival is 54%, and in patients with metastatic disease, the survival rate is 16% for 5 years. The effect of size on survival was then investigated for all patients with non-metastatic sarcomas at diagnosis. We have shown no significant correlation of duration of symptoms with size. However, it is known that the most common locations include the uterus, limbs, and the trunk of the body (most often in the retroperitoneal area). Persson BM, Rydholm A. Soft-tissue masses of the locomotor system. and Clipart.com. Histological necrosis after chemotherapy, resection margins and local recurrence were excluded from our study as they are not parameters that are available at diagnosis. Copyright 6). Medical professionals and health organisations are thought to confer the greatest source of delay in diagnosis rather than a patients duration of symptoms. will also be available for a limited time. Overall, the 5-year survival rate for soft tissue sarcomas is about 65%. The American Cancer Society is a qualified 501(c)(3) tax-exempt organization. In addition, tumors between 10 and 15 cm metastasized in 49% of cases, and tumors larger than 15 cm but less than 20 cm metastasized in 58% of cases. Median duration of symptoms in soft tissue and bone sarcomas influenced by patients age category, tumour size and the presence of metastasis at diagnosis. Doctors also use a cancer's stage when talking about survival statistics. Around 6 out of 10 people with Ewing sarcoma live at least 5 years after being diagnosed. Death within one year does not correlate with a long history but is associated with advanced disease at diagnosis. Hazard ratios were estimated using a Cox model with relevant values entered either as continuous variables (e.g. Similar trends have been found in another study.14 Of these patients with metastasis, 70% were pulmonary, 13% having multiple metastasis. One-year mortality rates at our institution for sarcoma between 1980 and 2010, This study uniquely reports the 1-year mortality of STS and BS over a 25-year period as well as the factors that affect 1-year survival following diagnosis. But you're not alone. Soft tissue sarcoma patients who survived over one year reported a longer duration of symptoms preceding diagnosis than those who died (median: 26 vs 20 weeks, p <0.001). This can be done with: Radiation therapy: High-energy X-rays are directed at the tumor to kill cancer cells. Testicular cancer: perils of very late presentation. Our routine follow-up imaging for STS includes a chest x-ray and BS patients also have bone radiography. Risk factors for survival and local control in chondrosarcoma of bone. Public health education to raise awareness and prompt earlier recognition of smaller tumours with lower rates of metastasis and reduced perioperative morbidity may enhance sarcoma survival. The next section in this guide is Medical Illustrations. CONSULT A DOCTOR ON ALL MEDICAL DECISIONS.WRITTEN INFORMATION IS AVAILABLE ON REQUEST. Widhe B, Widhe T. Initial symptoms and clinical features in osteosarcoma and Ewing sarcoma. Dates and cause of death recorded on the database were verified by Public Health England, which records clinical and mortality data for all patients with sarcomas in England. This rates tumors from the mildest to most severe stages, and the system looks like this: The term grade applies to the changes in the tissue, and so a low-grade tumor is one in which cells have not differentiated much from the original tissue. However, these patients tended to have smaller, lower grade and more superficial tumours. The researchers collected a lot of data on patients, including age, tumor size, depth, tissue from which the sarcoma was formed, and the area in which it appeared. It is estimated that 5,130 deaths (2,740 men and boys and 2,390 women and girls) from this disease will occur in the United States this year. sharing sensitive information, make sure youre on a federal One hundred and ninety-four (32%) of all sarcoma patients presenting with synchronous metastases died within one year of diagnosis, with a larger OR in STS than in BS (7.08 vs 3.37). Making Strides Against Breast Cancer Walks. Leiomyosarcoma And Power Morcellators. BY USING THIS WEBSITE, YOU AGREE TO OUR PRIVACY POLICYANDTERMS OF USE.MAIN OFFICE; HOUSTON, TEXAS. To date, one-year survival has not been stratified in this way although numerous authors have attempted 510-year models, highlighting the importance of tumour location, histological grade, tumour size, metastasis and local recurrence.2325 For example, a 40-year-old patient with a large, deep, high grade synovial sarcoma of the trunk has a greater than 80% probability of sarcoma specific death within 12 years.23, With increasing emphasis on early diagnosis and the use of one-year mortality as a proxy for this, we feel that further research in this area to create a nomogram for death at one year will be valuable to clinicians, patients and uniform research reporting. The mean size of all sarcomas at presentation was 10.7 cm and did not vary significantly between the main diagnostic categories (soft tissue sarcomas, 10 cm; osteosarcoma, 11.3 cm; chondrosarcoma, 11.7 cm; Ewing's sarcoma, 11.2 cm) whilst the range was from 0.2 cm to 45 cm. The smaller the size at diagnosis, the lower the risk of the patient having metastasis and the better the chance of survival. Learn more On this basis, it would seem sensible to identify a common, everyday object, slightly less than 5 cm to act as a focus for people's attention to raise awareness of possible malignancy. . . Before The Symptoms of Ewing's SarcomaFrequent Symptoms. Symptoms of Ewing's sarcoma include bone pain, weakness, fever, and sometimes a visible lump on the bone.Rare Symptoms. Additional symptoms of Ewing's sarcoma depend on the location of the tumor and how advanced the cancer is.Complications. When to See a Healthcare Provider. While we have not shown that delay in diagnosis (as measured by duration of symptoms) is a useful prognostic factor at one year for either BS or STS, this study has demonstrated that TNM stage is a useful predictor. Patients treated prior to that date had data recorded retrospectively. Whether you want to learn about treatment options, get advice on coping with side effects, or have questions about health insurance, were here to help. This can involve taking a biopsy from a single local tumor and looking at its cells. Individual histological subtype mortality rates are reported in Table1, with variation in outcome between histological subtypes in STS and BS. government site. Studies have shown that lung metastasis is best treatable. The median size for all tumours was 10 cm. Johnson GD, Smith G, Dramis A, Grimer RJ. 2022 American Cancer Society, Inc. All rights reserved. However, the validity of prognostic factors at the time of diagnosis varies with time and survival. Tel / Whatsapp / Viber +972 54 803 45 32 info@resultmed.com, ResultMed services for international patients are authorized by the Israeli Ministry of Health and provided in accordance with its regulations, 2022 Resultmed. Kolovich GG, Wooldridge AN, Christy JM, et al.. A retrospective statistical analysis of high-grade soft tissue sarcomas, Prognostic factors in soft tissue sarcomas: the Aarhus experience, Incidence and survival of malignant bone sarcomas in England 19792007, Annals of The Royal College of Surgeons of England, http://www.england.nhs.uk/resources/resources-for-ccgs/out-frwrk/dom-1/. It's But this can vary and some people live much longer. This often means it is not possible to remove the tumor because of its location, size, or the organs it involves. About 60% of sarcomas are found as a localized sarcoma. 8). Whether you or someone you love has cancer, knowing what to expect can help you cope. Having a child being treated for cancer can feel overwhelming for any family. What is the life expectancy of someone with Ewing sarcoma? The overall 5-year survival rate for people with a Ewing tumor is 62% . If the tumor is found only in the area it began (called localized), the 5-year survival rate is 82%. You can help reduce your risk of cancer by making healthy choices like eating right, staying activeand not smoking. How doctors treat Ewing sarcoma depends on: The types of treatment used include some or all of these: Chemotherapy:Chemotherapyoften is given first to shrink the tumor, improve pain, and stop the spread of cancer. Talk with your health care team for more information regarding your specific diagnosis. Generally, LMS is a very aggressive disease that is difficult to treat with chemotherapy or radiation alone. This text is partly based upon a Hunterian Oration delivered at the Annual Meeting of the British Orthopaedic Association, September 2004. These factors are largely the same as those known to be important in predicting overall survival.2,12,15 Patients with advanced tumours at diagnosis (ie large, high grade and with metastases) have the worst prognosis, particularly when coupled with increasing age and proximal location. The site is secure. STS patients who died within one year tended to have a shorter duration of symptoms, even when this was stratified by stage (p<0.001). A useful size to rememberany lump bigger than this should be considered malignant until proved otherwise. The 5-year survival rate for people with locally advanced sarcoma is 56%. Statistics adapted from the American Cancer Society website and the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) Program. To find support, talk to anyone on the care team or a hospital social worker. National Library of Medicine Percent means how many out of 100. It is a simple step from here to suggest that any new guideline for awareness of possible malignancy in a lump, is simply to state: if a lump is bigger than a golf ball, consider it malignant until proved otherwise (Fig. [contact-form-7 id="262" title="Modal Form"], Leiomyosarcoma Treatment by Metastatic Site, Desmoplastic Small Round Cell Tumor (DSRCT), Leiomyosarcoma Treatment Side Effects, Leiomyosarcoma Treatment Radiation Therapy, Leiomyosarcoma Treatment Chemotherapy, 1A low grade/less than 5cm in size/can be superficial or deep/no metastatic disease, 1B low grade/more or less than 5 cm in size/superficial/no metastatic disease, 2A low grade/more or less than 5 cm in size/deep/no metastatic disease, 2B high grade/less than 5 cm in size/can be superficial or deep/no metastatic disease, 2C high grade/more or less than 5 cm in size/superficial/no metastatic disease, 3 high grade/more or less than 5 cm in size/deep/no metastatic disease, 4 any grade/any size/any location/metastatic disease. Learn more It is important to remember that this information can not predict the exact chances of survival and recovery of a particular patient. The mean size of tumours undergoing limb salvage was 10.2 cm compared to 12.1 cm for those having an amputation (t-test, P < 0.002). Federal government websites often end in .gov or .mil. It is a frequent observation that sarcomas present late and many will have reached a considerable size by the time of diagnosis. This means the estimate may not reflect the results of advancements in how soft-tissue sarcoma is diagnosed or treated from the last 5 years. One-year mortality in bone and soft tissue sarcoma patients is easy to measure, and could be a proxy for late presentation and therefore a potential performance indicator, similar to other cancers. If the doctor diagnoses Ewing sarcoma, the child will have other imaging tests to see if the cancer has spread to any other part of the body. You will also read general information on surviving the disease. Ewing sarcoma is a cancerous tumor that can happen in any bone in the body, but most often happens in bones of the arms, legs, rib, spine and pelvis. 3). A long duration of symptoms has been shown to correlate weakly with good prognosis.6 This study confirms the suggestion that this benefit is probably due to the fact that patients with a long duration of symptoms have a greater probability of having a low-grade tumour.7 Indeed, there may be an inverse relationship between symptoms and survival as some high-grade, rapidly growing tumours will present very quickly yet prove fatal whilst slow growing tumours with low metastatic potential may have a long duration of non-specific symptoms prior to the diagnosis being made. It is still premature to assess whether this guidance is resulting in tumours being detected earlier but it is certainly helping to raise the suspicion of potential malignancy in lumps and bumps. Learn more in the Stages and Grades section. Fortunately, among the major cancer types, there has been a consistent increase in one-year survival. Then those in the lower extremities, inside the trunk, chest and neck, inside or behind the abdominal cavity, and finally in the head and neck region. In general, cancer statistics often include the 5-year survival rate for a type of cancer. Access to the advanced medical expertise and technologies. There are multiple reasons why patients present late. You also can find information and support online at: Note: All information is for educational purposes only. In some cases, when the primary tumor and metastasis can be completely removed, recovery can be achieved even after metastasis. Early detection, surgical removal, and aggressive follow up can provide patients with an impressive prognosis, and so it is best for patients to head to a physician at the first sign of any symptoms relating to LMS condition. Use the menu to choose a different section to read in this guide. But with the combination of treatments available and powerful new therapies on the horizon the outlook for kids with advanced disease is improving. There was no association found between size and age category for bone tumours; however, there was a very significant trend for younger patients to present with smaller soft tissue sarcomas than older patients (Fig. The 5-year survival rate tells you what percent of people live at least 5 years after the cancer is found. Many resources are available to help you and your child. All rights reserved worldwide, Sarcoma, Soft Tissue - Medical Illustrations . The estimate comes from annual data based on the number of people with this cancer in the United States. For soft tissue tumours, the proportion with metastases also varied according to the size of the tumour at presentation and rose from 3% in those with tumours < 5 cm to 18% in those with tumours > 25 cm (Fig. The Memorial Sloan Kettering Cancer Center has developed a survival scale based on the results of studies of 2,163 patients who have been treated at the center surgically for many years. The data for patients with bone and soft tissue sarcomas have been analysed using Statview to investigate size of tumours and duration of symptoms at presentation related to how they present, how they were treated and outcomes. One of the most important factors in this study is the area in which the sarcoma begins. The median duration of symptoms from first patient-identifiable abnormality to diagnosis was 16 weeks for bone sarcomas and 26 weeks for soft tissue sarcomas. Delays in referral of soft tissue sarcomas. It helps determine how serious the cancer is and how best to treat it. Because of their rarity, many doctors will never (knowingly) see one in a life-time of practice. Become a volunteer, make a tax-deductible donation, or participate in a fundraising event to help us save lives. Survival for all stages and types of soft tissue sarcomas Generally, for people with soft tissue sarcoma in the UK: 75 out of 100 people (75%) survive their cancer for 1 year or more after It is also important to remember that statistics on the survival rates for people with soft-tissue sarcoma are an estimate. THE MEYER LAW FIRM WILL MAINTAIN JOINT REPRESENTATION AND JOINT RESPONSIBILITY FOR CLIENTS AND CASES,BUT CASES AND CLIENTS WILL LIKELY BE REFERRED TO OTHER LAW FIRMS FOR PRINCIPAL HANDLING. It also investigates whether death within one year of sarcoma diagnosis could be due to delay in presentation and its validity as a proxy for advanced stage at diagnosis. It is disappointing that size at diagnosis for bone and soft tissue sarcomas has not changed significantly over the last 25 years19 and this has been reinforced by our demonstration that 1-year survival rates have not improved either. Amputation or limb salvage in patients treated by neoadjuvant chemotherapy. NHS England, Earlier diagnosis of bone and soft-tissue tumours. Catching cancer early often allows for more treatment options. Ewing sarcoma is more common in people of European ancestry. Find out how Ewing tumors are tested for, diagnosed, and staged. Overall, 595 patients (12%) died within one year of diagnosis. . Fiorenza F, Abudu A, Grimer RJ, Carter SR, Tillman RM, Ayoub K, et al. Recent papers by de Boer et al.1 and others2 about late presentation of testicular cancer caused me to reflect on the similarities with another rare type of cancersarcomas. There has been a significant decrease in the size of soft tissue sarcomas presenting over the course of 20 years, but at 9.3 cm this is still a relatively large size, particularly when it is appreciated that the average size of breast cancer diagnosed is 2.1 cm.3. In the U.S. each year there are only a few thousand cases of LMS diagnosed, and these can range very widely in terms of their location and severity. We have confirmed that tumour size is an important factor in predicting one-year mortality and the larger the tumour at diagnosis, the worse the chances of survival. Below are some of the resources we provide. We report, for the first time, one-year mortality rates for STS and BS. Details of size at presentation was available for 1460 patients with newly diagnosed sarcomas. Research. One-year mortality is now a proxy for early/late stage at diagnosis for major cancer groups, where improvements in one-year mortality reflect increasing proportions of patients having an earlier diagnosis.1 Late diagnosis is considered a key reason for inferior sarcoma survival rates in England compared with Europe, with strategies employed to reduce symptom duration by enhancing diagnostic services and raising public awareness.4 Domain 1 of the National Health Service outcomes framework aims to prevent people from dying early.4 It emphasises the need to treat people in an appropriate and timely fashion. Prompt coordination of doctor consultations, doctor second opinion, diagnostics and medical treatment in Israel. According to this study, sarcomas smaller than 2.5 cm at the time of diagnosis had a 6% chance of metastasis. Cancer.org is provided courtesy of the Leo and Gloria Rosen family. Since complete removal of the sarcoma by surgery is the most effective method of treatment, any restriction in the operation adversely affects the chances of recovery. Clasby R, Tilling K, Smith MA, Fletcher CD. It therefore remains true that it is very important for prognosis in both BS and STS cases. Has it any effect on the stage of disease? Kaplan Meier survival curve showing survival for all sarcomas split by duration of symptoms being more or less than one year. Here you can see if there is any natural remedy and/or treatment that can help people with Ewings sarcoma Patients with deeper tumours had poorer outcomes, with larger size at presentation. The .gov means its official. Prognostic factors in Ewing's tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing's Sarcoma Study Group. For many cancers, one-year mortality following diagnosis is a reflection of either advanced stage at diagnosis, multiple co-morbidities and/or complications of treatment. Comprehensive information for people with cancer, families, and caregivers, from the American Society of Clinical Oncology (ASCO), the voice of the world's oncology professionals. Patients with BS also had radiography of the bone treated. Is fruit a useful indicator of the size of an object? A prospective computerised database was established at the Royal Orthopaedic Hospital Oncology Service in 1986 since when all patients referred to the unit have had data collected on patient, tumour, treatment and outcome factors. Duration of symptoms did not correlate with size but patients with symptoms > 1 year had a slightly better prognosis than those with a shorter duration. The site is secure. The stage of a Ewing tumor describes how much cancer is in the body. However, even deep soft tissue sarcoma averaged over 10 cm in size at diagnosis. Learn more about understanding statistics. Bethesda, MD 20894, Web Policies For tumors exceeding 20 cm, the probability of metastases is 83%. LMS is a cancer of the soft tissue, and because it impacts the involuntary muscles it can appear almost anywhere on the body. These include slow tumour growth, lack of pain or a palpable mass, deep location, doctor inexperience and socioeconomic factors.7,18 We were not able to demonstrate that a prolonged duration of symptoms (delay in presentation) led to a worse outcome at one year as patients with a long history often have slow growing, low grade tumours.19 On the contrary, patients with a longer history had better outcomes at one year, even when the effect of grade was taken into account. However, when the cancer has spread to other organs, Chemotherapy-related side effects can include: Ewing sarcoma has the best chance of being cured when it's treated by experts in pediatric cancer treatment. For soft tissue sarcomas, it is clearly easier to detect one when it is subcutaneous and this is reflected by the size difference between deep and subcutaneous tumours. Results expressed as hazard ratios (i.e. Before Early diagnosis, to reduce size at presentation and decrease the incidence of synchronous metastasis, is fundamental to improving prognosis, with superior resection margins and reduced surgical complications in smaller tumours.5,6 Delays in diagnosis of both bone and soft tissue sarcomas are common and multifactorial; they are often due to public and professional low awareness as well as the non-specific nature of many symptoms.7,8, Reducing one-year mortality is an important issue following the publication of national guidelines, where the performance of cancer services are under increasing scrutiny.9,10 Early diagnosis and identification of high risk patients is a large facet of this work. Soft tissue sarcoma one-year mortality rates influenced by tumour and patient variables at the time of diagnosis, OR = odds ratio; CI = confidence interval; TNM = tumour, lymph node, metastasis, Bone sarcoma one-year mortality rates influenced by tumour and patient variables at the time of diagnosis. The https:// ensures that you are connecting to the It is important to note that the length of time a person lives with a sarcoma depends on many factors, including the type of sarcoma, the size, where it is located, and how quickly the tumor cells are growing and dividing, called the grade. The high-grade tumors are those that do not have the best prognosis simply because they are much more likely to spread quickly. About 15% of sarcomas are found in a metastatic stage. ONCE YOU BECOME A CLIENT OF THE FIRM, INFORMATION REGARDING YOUR CLAIM MAY BE TRANSMITTED IN COMPLIANCE WITH HIPAA AND HOUSE BILL 300. Older patients with a BS (but not a STS) also had a longer duration of symptoms prior to diagnosis (p<0.05). Some kids may need to return to the hospital between treatments if they have side effects, like fever or infection, or if they need a blood transfusion. We couldnt do what we do without our volunteers and donors. Abstract Progress in the treatment of Ewing's sarcoma, the second most common bone tumour in children and adolescents, has improved survival from about 10% in the period before chemotherapy was introduced to about 75% today for patients with localised tumours. Gray JM, Khan MT, Grimer RJ, Pynsent PB. When systemic, though, these are the only treatment options. For instance, analysis of median duration of symptoms was limited by the small sample size once divided into diagnosis subtype. Studies have shown that those patients whose tumor develops in the upper limbs have higher chances of recovery. Table 1 One-year mortality rates and duration of symptoms (DOS) of individual sarcoma subtypes in bone and soft tissue sarcomas. Metastases are secondary cancers of the original sarcoma, they are formed when the cells of the primary tumor move through the human body to other organs. Only 8% of those patients with small (< 5 cm) tumours required amputation compared to 39% of those with tumours > 25 cm. by Cook Children's Health Care System, Fort Worth, Texas, Late Effects of Cancer and Cancer Treatment, Side Effects of Chemotherapy and Radiation. Patients with a longer duration of symptoms did appear to have a better prognosis and this was apparent when a cut off was taken both at 6 months and 1 year (Fig. There was also a significant difference in size at presentation of subcutaneous and deep soft tissue sarcomas, with subcutaneous soft tissue sarcoma being 5.9 cm and those deep to the deep fascia being 10.9 cm (P > 0.0001). At diagnosis, a number of factors are available to the clinician that can facilitate estimation of one-year mortality risk on an individual patient basis. It is estimated that 5,130 deaths (2,740 men and boys and 2,390 women and girls) from this disease will occur in the United States this year. Sarcomas are a rare heterogeneous group of tumours that often present late with large size at diagnosis and long symptom duration. The exception to this was chondrosarcomas where patients had an average duration of symptoms of Help make it a reality. Processing prognostic factors into a model where a single survival estimate can be obtained is more useful to the patient than ORs when counselling their expectations and making informed decisions. STS cases were further divided into superficial or deep tumours relative to the deep fascia. There are approximately 450 new bone sarcomas a year diagnosed in the UK and about 1500 soft tissue sarcomas. This may not be surprising as previous work has demonstrated that a long duration of symptoms in STS patients is related to lower grade, which in turn has a better survival.16. - eMedicineHealth Patients were subdivided accordingly into large size (>8cm for BS and >5cm for STS) or small size (as defined by the TNM [tumour, lymph node, metastasis] system).13 In cases where a previous inadvertent excision had been carried out, the pathology report indicated the size. HHS Vulnerability Disclosure, Help This was not the case for BS cases, where duration of symptoms did not affect survival. Conditional survival taking into account response to adjunctive therapy, local recurrence and resection margins is important to long-term survival estimates.14,22. About 18% of sarcomas are found in a locally advanced stage. A patient with a > 25 cm tumour has an 8.5 times greater risk of dying than a patient with a tumour < 5 cm at diagnosis.