When you are told you have prostate cancer and begin looking for treatment options, you may be concerned about life expectancy and quality of life. The chart below shows the cancer survival rates of 95 metastatic prostate cancer patients who were diagnosed between 2000 and 2009. Of the CTCA metastatic prostate cancer patients shown in the above chart, the estimated survival rate at six months was 95%.
SEER is the only authoritative source of population-based information about cancer incidence and survival in the United States that includes the stage of cancer at the time of diagnosis and patient survival data. The objective of this analysis was to see how long each group of patients survived after their diagnosis.
The independent biostatistician computed the survival outcomes of metastatic prostate cancer patients from the CTCA database and metastatic prostate cancer patients from the SEER database who were diagnosed between 2000 and 2009.
The chart below shows the cancer survival rates for a group of 156 metastatic prostate cancer patients who were diagnosed between 2000 and 2011.
Of the CTCA metastatic prostate cancer patients shown in the above chart, the estimated survival rate at six months was 96%. At Cancer Treatment Centers of America, we understand that you may also wish to see the survival rates of the group of metastatic prostate cancer patients reported in the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute.
Therefore, we asked an independent biostatistician to analyze both the survival rates of the group of CTCA patients and the group of patients included in the SEER database. We also want to be sure you understand that cancer is a complex disease and each person’s medical condition is different; therefore, CTCA makes no claims about the efficacy of specific treatments, the delivery of care, nor the meaning of the CTCA and SEER analyses.
This analysis included prostate cancer patients from CTCA who were diagnosed from 2000 to 2011 (including 2000 and 2011) with a primary tumor site (as coded by ICD-O-2 (1973+)) of C619, and were considered analytic cases by the CTCA. Primary tumor sites (as coded by ICD-O-2 (1973+)), date of initial diagnosis, date of last contact, year of initial diagnosis, age of initial diagnosis, gender, vital status, and cancer histologic type as coded by the ICD-O-3.
The database from the CTCA cohort was prepared by the CTCA cancer registrars from the following four hospitals: Southwestern Regional Medical Center hospital, Midwestern Regional Medical Center hospital, Eastern Regional Medical Center hospital, and Western Regional Medical Center hospital. The SEER program of the National Cancer Institute is an authoritative source of information on cancer incidence and survival in the United States.
This analysis included prostate cancer patients from the latest SEER Limited-Use Database (as of 2014) who were diagnosed from 2000 to 2011 (including 2000 and 2011) with a primary tumor site (as coded by ICD-O-2 (1973+)) of C619. Primary tumor sites (as coded by ICD-O-2 (1973+)), survival time recode as calculated by the date of initial diagnosis and the date of death or the follow-up cutoff date, year of initial diagnosis, age of initial diagnosis, gender, vital status, and cancer histologic type as coded by the ICD-O-3.
In order to make a meaningful survival analysis, basic cancer and patient characteristics such as age at initial diagnosis, year of initial diagnosis, cancer stages, and cancer primary sites were first analyzed for both the CTCA and SEER samples. For example, if a specific primary tumor site had patients in only one database, none of those patients were used in the analysis. The survival outcome from the CTCA database was defined as the time from the initial diagnosis to death and computed in number of years as the difference between the date of death and the date of initial diagnosis divided by 365.25. For each survival outcome from each database, the survival curve, defined as the probability of cancer patient survival as a function of time after the initial diagnosis, was estimated by the nonparametric product-limit method[1]. Covariates such as age at initial diagnosis and year of initial diagnosis could affect the survival of prostate cancer patients.
We understand you may be feeling overwhelmed with questions and concerns about your type of cancer and what it all means.
Explore our cancer hospitals, which house the latest treatments, technologies and integrative oncology services under one roof. Discover our patient-centered approach, and how you get all your questions answered in a single visit by a dedicated team of cancer experts. Survival StatisticsOne of the first questions that most patients ask their doctor or ask themselves is “How long do I have?” Cancer and dying are closely linked in our minds, and, whether we want to ask the question or not, worry about dying from colorectal cancer is always in the back of the mind of patients and caregivers. Doctors use different terms in discussing statistical chances for survival. Remember that these are only statistics and you are an individual! Statistical information about survival helps in developing new treatments for cancer and deciding their effectiveness. Five-Year Relative Survival: the percentage of patients alive at five years, not including deaths from other illnesses. Median Overall Survival: the time at which 50 percent of patients are still alive after a diagnosis or particular treatment.
Median Disease-Free survival: the time at which 50 percent of patients are still alive without evidence of tumor recurrence. Doctors give survival statistics based on historical information, so the numbers do not reflect the current standards of care or recent improvements in chemotherapy, surgery and radiation therapy. This survival chart offers one example of why survival statistics don’t always predict your case or display the most recent information. This is significant because cancer recurrence is most common within three years of diagnosis – so most of the people who survived are probably cancer-free.
Additionally, while there are no cures for metastatic cancer, new treatments have increased the time people live with advanced disease – and this chart does not show that information. Unhappily, we don’t yet have a cure for all metastatic CRC patients, although some stage IV patients have been cured, particularly those with surgically removable metastases only to the liver. CLINICAL PRESENTATIONCervical carcinoma may present with a variety of anatomic configurations.
Chemotherapy which involves the administration of intravenous drugs that are specifically designed to destroy the cancer cells. Stem cell transplant wherein the diseased bone marrow is replaced with a health bone marrow.
Hodgkin’s lymphoma can occur in any age group, but usually tends to affect young adults and adolescents and more men as compared to women. In order to better understand the survival rate for lymphoma, doctors have devised the five year survival rate for the condition. The overall five year survival rate has increased from around forty percent in sixties to around 90 percent in the early 2000s. As per survey conducted on British patients, the five year survival rate for men and women in the age group 15 to 49, is 87 % and 92 percent respectively; and for those over 70, it is 27 % and 32 % respectively. Results of Subgroups Defined by Number of Involved Axillary Lymph Nodes in PMRT Trials (Ref. Danish 82b trial evaluated the impact of axillary dissection on the LRF rate in patients not undergoing PMRT. Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-Share Alike 2.5 License. At Cancer Treatment Centers of America® (CTCA), we believe you have the right to know our statistics for prostate cancer treatment outcomes, so you can choose the best cancer care for you and your family. Therefore, we asked an independent biostatistician to analyze the survival results of CTCA® patients.
This means that six months after their diagnosis, 95% of the patients in this group were still living.
Therefore, we asked the same independent biostatistician to analyze both the survival rates of CTCA patients and those of patients included in the SEER database. Therefore, SEER is currently the most comprehensive database for the analysis of CTCA results and national results. Our fifth hospital, located near Atlanta, Georgia, was not included because it was not open to patients until August 2012.
Across all the 11 cancer types whose survival results are presented on the CTCA website, 0.48% of the CTCA patients included in the analyses were only diagnosed by CTCA and received no initial course of treatment from CTCA. In both cases, the patients had been diagnosed with metastatic or distant cancer – cancer that had traveled from the primary site (prostate) to one or more distant sites in the body where it continued to grow.
These factors significantly reduced the size of the CTCA sample, which means that the estimates reflected in the survival chart may be subject to high variation and may not be replicated in the future when we have a larger CTCA sample for analysis.
Not all cancer patients who are treated at a CTCA hospital may experience these same results. This means that six months after their diagnosis, 96% of the patients in this group were still living. SEER is a source of population-based information about cancer incidence and survival in the United States that includes the stage of cancer at the time of diagnosis and patient survival data. The independent biostatistician computed the survival outcomes of metastatic prostate cancer patients from the CTCA database and metastatic prostate cancer patients from the SEER database who were diagnosed between 2000 and 2011. More specifically, the SEER Limited-Use Database contained a combination of three databases. The survival outcome from the SEER database was provided by the SEER Limited-Use Data File as the number of completed years and the number of completed months.
Formal statistical analyses of the prostate cancer survival distributions between the CTCA database and the SEER database were conducted by the nonparametric logrank test and Wilcoxon test as well as the likelihood ratio test[1]. Similar estimates were also computed to estimate the difference of the survival rates at these time points between the two cohorts. Therefore, additional adjusted analyses were completed on the survival outcomes between the CTCA and SEER samples after adjusting for the effects of these covariates.
First, although a large cancer sample was available from the SEER program across many geographic regions in the United States, both samples, including the sample from CTCA, are convenience samples.
Survival, even when cancer has spread and is at an advanced stage, is remarkably individual. But, survival predictions for individuals are not always reliable and they can significantly add to your worry. Improvement of the treatments you get today recently increased the relative survival for people diagnosed at stage III, and the length of time that people with metastatic cancer will live.
The chart shows that 70 percent of the people diagnosed with stage III CRC from 2003-2009 were alive after five years. In 1999, the average survival after a diagnosis of metastatic cancer was nine months, while today it is almost three years.
Stephen Gould, an evolutionary biologist, wrote about the challenge of applying “average” statistics to an individual patient in his essay The Median Is Not The Message.
As tumors enlarge, they can produce lesions that are primarily exophytic, infiltrative, or ulcerative. It is believed that mutations in the DNA of B cells results in the development of lymphoma. The procedure involves the use of high doses of radiation therapy and chemotherapy to destroy the cancer cells. It indicates the percentage of patients who have survived for at least a period of five years after initial diagnosis. But would only treat first 3 intercostal space and only if heart was not in the field and lung volume was limited.
SEER collects information on cancer incidence, prevalence and survival from specific geographic areas that represent 28% of the population of the United States. In both cases, the patients had been diagnosed with distant (metastatic) cancer as discussed above. The SEER Program is a comprehensive source of population-based information in the United States that includes stage of cancer at the time of diagnosis and patient survival data. Patients whose age at initial diagnosis fell into the overlap of the two ranges from the CTCA and SEER samples were included in the survival analysis. These were then converted to the number of years by dividing the number of total months by 12. Because the estimated survival curves might not estimate the survival probability at these specific time points, survival rates from the closest observed survival times were used.


The nature of these convenience samples prevents a causal interpretation of the statistical inferences. And treatment options are improving all the time.  Your doctor may be able to provide you with statistics for people with diagnoses similar to yours, but your case is your own! Although radiation alone can cure many patients with local-regionally advanced disease, recent studies have demonstrated that concurrent delivery of cisplatin-containing chemotherapy can improve the rates of local disease control and survival.5, 6, 7, 8, 9 However, treatment modality and technique must be individualized on the basis of clinical, anatomic, and social factors. The anatomic distortion produced by these lesions is an important consideration in determining the optimal sequence of therapy. However, this cannot be generalized as lymphoma patients can die due to other complications and diseases. It is also possible that the SEER database may contain some of the CTCA cancer cases that were part of the analysis.
This means the cancer had traveled from the primary site (prostate) to one or more distant sites in the body where it continued to grow. All comparative survival analyses were conducted separately for the mild to moderate cancer stage and the advanced cancer stage (defined by the SEER Summary Stage of 7) using patients from the CTCA and SEER databases.
For these patients who were still alive or lost to follow-up at the time of entering the databases, their survival time was treated as statistically censored[1] at the difference between the date of last contact and the date of initial diagnosis.
Because five-year survival rates have been popularly used in many cancer survival reports, five-year survival curves were also obtained by treating those who survived more than five years after the initial diagnosis as statistically censored at five years.
Second, although some types of matching, as described above, were implemented to select the appropriate SEER and CTCA comparison samples, the distributions of important covariates such as age at initial diagnosis, race and year of initial diagnosis were not exactly the same between the CTCA sample and SEER sample. Optimal treatment selection always requires close cooperation between the patient’s referring physician, gynecologic oncologist, and radiation oncologist.
Large exophytic lesions usually necessitate an initial course of external-beam radiation therapy (EBRT) to shrink the tumor and allow close approximation of the intracavitary system to the cervix during subsequent intracavitary radiation therapy (ICRT). The relative five year survival rate is a comparison of the five year survival rate of the lymphoma patients against the general population with similar age and other characteristics and which is not affected by the disease. Because patients surviving more than five years remained part of the risk sets in the estimation of survival rates at any time within five years of diagnosis, the truncated survival curves were identical to the first portion of the complete survival curves. Hence, even with the adjusted analyses, the possible confounding of these factors to the analyses and results cannot be ruled out.
Lesions that originate in the endocervix may expand the cervix concentrically and become barrel-shaped. Another Cox proportional hazards model was also used to simultaneously adjust for the effects of both covariates (age at diagnosis and year of initial diagnosis) in the survival analysis.
Results of treatment with radiation therapy for carcinoma of the cervix Study FIGO Stage No. In such cases, initial EBRT is used to shrink the tumor so that it is within the range of the high-dose portion of the ICRT dose distribution. The tumor may spread beyond the cervix by direct extension, lymphatic involvement, or hematogenous metastasis. Third, the survival analyses were based on the statistical comparisons of the rate of death from all possible causes, not solely the cancer-specific death. The tumor may extend directly to involve the vagina, uterine body, paracervical tissues, and, infrequently, the bladder or rectum.
Data from CTCA are not available for a statistical comparison on cancer cause-specific death rates. Microscopic vaginal involvement may extend some distance beyond visible or palpable disease, and palpable discontinuous vaginal involvement can occur when the disease spreads along submucosal lymphatic channels. Although the tumor may extend directly to adjacent tissues, discontinuous involvement may also occur by lymphatic metastasis to the lymphatics of the broad ligament. Tumor invasion of the periureteral tissues sometimes causes ureteral obstruction and hydronephrosis. Although the rate of regional metastasis is strongly correlated with tumor size and stage, even small cancers may involve regional lymphatics.
The tumor may then progress secondarily to involve the common iliac, precaval, and para-aortic nodes.
A history of multiple abdominal operations or pelvic inflammatory disease is associated with an increased risk of late treatment-related complications. Although these tumors have been subdivided in terms of cell size, grade, and the degree of keritinization, the subtypes of squamous carcinoma seem to have little impact on prognosis. In one of the largest studies comparing outcomes in women treated with radiation for adenocarcinomas or squamous carcinomas of the cervix, Eifel and coworkers12 reported histology to be an independent predictor of poor prognosis, with more frequent distant metastasis and poorer survival in patients with adenocarcinoma; pelvic disease control rates were similar for squamous and adenocarcinomas.
They are histologically similar to small cell neuro-endocrine carcinomas originating in other sites and frequently behave very aggressively, with rapid widespread dissemination.15, 16, 17 Lymph-vascular space invasion and lymph node involvement are frequently present at diagnosis. Although patients with small-cell carcinomas sometimes have dramatic responses to neoadjuvant chemotherapy,15 the impact of chemotherapy on survival has not been established, and there is no evidence that radiation therapy doses can be decreased without increasing the risk of local failure.Determination of Extent of Disease The staging system for cervical cancer recommended by the International Federation of Gynecology and Obstetrics (FIGO) is shown in Table 2.
The system categorizes patients in terms of the extent of clinically detectable local disease.
However, it does not include some important predictors of outcome, particularly lymph node status. Tumor size, another important predictor of outcome (Table 3), was only recently incorporated into the staging system. In an effort to maintain consistency and international relevancy, the FIGO system is based on limited examination methods, including palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous pyelography, chest radiography, and skeletal radiography.18 FIGO specifically prohibits the use of surgical staging and other studies that may not be accessible to patients with limited resources. FIGO staging system for cervical cancer (1994)Stage 0Carcinoma in situ, intraepithelial carcinoma. Extension to the corpus should therefore be disregarded.A patient with a growth fixed to the pelvic wall by a short and indurated but not nodular parametrium should be allotted to stage IIb.
It is impossible, at clinical examination, to decide whether a smooth and indurated parametrium is truly cancerous or only inflammatory. When abnormalities are found, they can be confirmed with fine-needle biopsy.Although these radiologic and surgical studies are often useful in selecting the best treatment for patients, they should not be used to alter the FIGO stage.
Inconsistent use of such information to alter the assigned stage in conflict with FIGO rules only makes it more difficult to compare results between institutions.Surgical staging of lymph nodes is unquestionably the most accurate staging method but is invasive and can delay treatment of the primary lesion.
It should not be forgotten that even lymph node dissection does not identify all patients with nodal disease. The sensitivity of surgical lymph node evaluation depends on the nodes removed and on the surgical pathologist’s treatment of the specimen.
All patients should always have a clinical stage assigned preoperatively to facilitate comparison of experiences between institutions.TECHNICAL ASPECTS OF RADIATION THERAPYRadiation therapy for intact carcinoma of the cervix usually involves a combination of EBRT and brachytherapy (usually ICRT). The goal of treatment is to balance EBRT and brachytherapy in a way that maximizes the likelihood of local-regional tumor control while minimizing the risk of treatment complications. For many patients with local-regionally advanced disease, these treatments must also be carefully integrated with chemotherapy to achieve the greatest likelihood of cure.The primary goals of EBRT are to sterilize regional disease and to shrink central tumor to facilitate subsequent brachytherapy. The degree of tissue penetration achieved by a radiation beam is related to the energy of the x-rays delivered from the radiation source. One of the earliest sources used for EBRT was Co 60, which produced a relatively deeply penetrating beam. Because the radiation dose is proportional to the square of the distance from a source of radiation, tissues close to a source will receive a much higher dose than those farther away. The therapeutic advantage of ICRT always depends on the ratio of the distance between the sources and the tumor and the distance between the sources and critical normal tissues. Radium was first used to treat uterine malignancies shortly after its discovery at the turn of the century and was convenient because of its very long half-life (Table 4). These approaches are discussed in further detail in the Dose Rate section.Radiation Therapy Planning EBRT is used to shrink bulky endocervical tumors to bring them within the range of the high-dose portion of the ICRT dose distribution (Fig.
1), to shrink exophytic tumors that distort anatomy, and prevent optimal brachytherapy, and to sterilize disease (paracentral and nodal) that lies beyond the reach of the ICRT system. The dotted line represents the volume that would typically receive a minimum of 30 Gy from a 48-hour intracavitary treatment. Tumor cells in the periphery of the tumor may receive a dose inadequate to achieve central tumor control. An initial course of external-beam radiation therapy (EBRT) may shrink central disease and bring it within the volume treated to high dose with the intracavitary system. Perez and colleagues30) prefer to maximize the brachytherapy component of treatment and deliver the first ICRT treatment as soon as EBRT has shrunk the tumor sufficiently to permit good placement of an intracavitary system (with bulky tumors, this may still require 40 Gy or more of EBRT).30 Subsequent irradiation of the pelvic lymph nodes is done using anterior and posterior fields with a block that shields central structures that received the greatest dose from ICRT. Initial treatment of the whole pelvis to a total dose of 40–45 Gy provides a homogeneous distribution to the entire region at risk for microscopic disease and may produce somewhat more shrinkage of central disease before ICRT. In fact, both approaches have been in use for several decades and, when optimally employed, appear to yield excellent tumor control rates with acceptable complication rates. However, medical problems or morbid obesity may complicate surgery, and in such cases, ICRT alone yields good results. Some patients with very small stage IB disease (less than 1 cm) may also be treated with ICRT alone, particularly if there are relative contraindications to a course of EBRT.32 Patients who have relatively small lesions and a narrow vagina should be treated with ICRT first to optimize the brachytherapy portion of treatment before EBRT causes additional narrowing of the vaginal apex. A total dose (EBRT plus ICRT) of 50–55 Gy appears to be sufficient to sterilize microscopic disease in the pelvic nodes in most patients. Co 60 or 6–10 MV) are used, multiple-field techniques (usually anterior, posterior, and lateral fields) should be used to reduce the dose to subcutaneous tissues (Fig. Treatment technique and custom blocking must be carefully tailored to encompass the patient’s known disease and potential sites of microscopic disease. Today, treatment is usually planned using CT or MRI scans that may help the radiation oncologist define a target volume.
However, during treatment planning, it is important to take into account that the position of the cervix can move by as much as 3–4 cm with changes in bladder filling.
Comparative dose distributions from external-beam radiation therapy (EBRT) in a patient with an anterior-posterior diameter of 22 cm. Note the relatively high dose that must be delivered to superficial tissues in order to achieve the desired dose of 200 cGy to the deep pelvis. An 18-MeV beam gives a more favorable ratio between the dose to deep tissues and the dose to superficial tissues. In some cases, further sparing of superficial tissues may be achieved by delivering a portion of the dose with lateral fields (also with an 18-MeV beam).To treat the whole pelvis, treatment fields typically extend from the L4-5 interspace superiorly to the midpubis or to a line 4 cm below the lowest vaginal disease (Fig.
The lateral margins and shielding should be more generous if massive obesity reduces the reproducibility of the treatment setup.
An example of anterior (left) and lateral (right) fields with custom blocking that may be used in a four-field pelvic irradiation technique for treatment of carcinoma of the cervix. In this patient, the external iliac and common iliac lymph nodes are visible after injection of radiopaque dye for a lymphangiogram.
Custom blocks may be used to shield anterior small bowel, soft tissue, and, in some cases, low rectum on the lateral fields. Although 40–45 Gy is usually sufficient to control microscopic tumor in the pelvis, additional treatment must be given to control gross disease.
However, the fields may be extended superiorly if the para-aortic nodes are known to be involved or are believed to be at high risk for involvement. Because cervical cancer typically follows an orderly progression along the lymph node chain, the upper border is selected by balancing an estimate of the risk of disease at a given level against the expected morbidity from large-volume EBRT. This is probably sufficient if the patient has had a lymph node dissection with negative nodes above the level of involvement. Bulky or multiple nodes probably warrant greater extension of the fields, particularly if the patient has not had surgical evaluation of the nodes.


The Radiation Therapy Oncology Group (RTOG) 79-2042 compared pelvic irradiation with extended-field (upper border L1-L2) radiation therapy in patients with stage I or II disease. Analysis of this trial demonstrated a significantly better survival rate for patients who received prophylactic aortic irradiation in addition to pelvic irradiation and ICRT.
A second trial, performed by the European Organization for Research and Treatment of Cancer (EORTC),41 involved a similar randomization but had more extensive clinical staging of the abdomen (patients were required to have negative para-aortic nodes as determined by lymphangiography) and included patients with more advanced disease (bulky stage II or stage III). The locally advanced tumors included in this trial and the corresponding high local failure rate may have reduced the potential benefit of large-field irradiation. The relative benefit of prophylactic extended-field irradiation may also be reduced when more accurate evaluations of regional metastases are available. Today, prophylactic aortic irradiation is performed infrequently because a later RTOG trial6 found an even greater advantage from pelvic irradiation and concurrent chemotherapy.Although EBRT plays an important role in the treatment of cervical cancer, the high central dose delivered with ICRT is also an extremely important component of curative treatment of cervical cancer.
Patients should be treated with EBRT alone only in the rare case of massive, poorly responsive disease in which the uterine canal cannot be probed, even with ultrasound guidance. The applicator is loaded with radium or cesium in the patient’s room after the accuracy of placement has been verified radiographically and the patient has recovered from anesthesia. Remote afterloading units are now available with Fletcher-Suit-Delclos–type applicators. Fletcher-Suit-Delclos applicator modified for use with Nucleotron Selectron remote afterloading system.
Colpostats are designed to have the vaginal sources approximately perpendicular to the vaginal axis in order to minimize the dose to the bladder and rectum.
5 illustrates the influence of the inverse square law on the depth dose from colpostats and uterine tandems.
The radiation dose to a point in the pelvis depends on the amount of cesium in each source, the distance from each source to the reference point, and the length of time the radioactive sources remain in place. Optimal placement of the uterine tandem and vaginal ovoids produces a pear-shaped distribution laterally, delivering a high dose to the cervix and paracervical tissues and a reduced dose to the rectum and bladder (Fig. Intracavitary applicators for treatment of carcinoma of the cervix take advantage of the inverse square law. The dose delivered by a radioactive source varies inversely as the square of the distance from the source to that point. The influence of colpostat diameter on the ratio between vaginal surface dose and the dose 1 cm below the vaginal surface. With a 2-cm colpostat, the radium (or cesium) source is 1 cm from the vaginal surface and 2 cm from the deep submucosal point. For this reason, the larger diameter colpostats should be used whenever possible to optimize the ratio between the dose delivered to the vaginal surface and that delivered to deep paracolpal tissues. As the length of the source increases (keeping the overall activity of radium or cesium constant), the dose to the mucosa decreases and the dose at point B increases.
Because of this, the linear source used in a uterine tandem should be as long as the patient’s vaginal anatomy will permit. Dose distributions from a typical intracavitary system using a Fletcher-Suit-Delclos applicator modified for use with a Nucleotron Selectron remote afterloading system. This placement of the sources generates a dose distribution nearly identical to that produced when a 15-mg and two 10-mg linear radium sources are placed in the tandem and two 15-mg sources are placed in two small (2-cm diameter) colpostats.The manipulations necessary to optimize placement of the intracavitary system in different anatomic situations can only be learned with experience. To maximize the chance of local control in the treatment of bulky cervical tumors, treatment is prescribed to deliver the highest dose to the tumor that will not produce an unacceptable risk of major complications.
Because there may be a narrow margin between tumor control and normal tissue complications, the radiation oncologist must make every effort to optimize the intracavitary system to obtain a favorable ratio between the dose to the tumor and the dose to adjacent normal tissues. The vaginal ovoids are placed up against the cervix, centered on the cervical portio; on a lateral radiograph, this usually means that the colpostats are bisected by the tandem. The vagina is packed to displace the rectum and bladder away from the intravaginal sources and to keep the system in place. For patients who have received initial EBRT, the first intracavitary placement should be administered as soon as possible after completion of EBRT (usually 1–5 days). Excessive protraction of the overall treatment time will compromise its effectiveness.45, 46, 47Treatment Prescription and Dose Specification Methods of ICRT treatment prescription and dose specification have generally been developed empirically and differ significantly, making it difficult to compare experiences between institutions. There is no inherently correct way to specify the inhomogeneous radiation dose distribution delivered with an intracavitary system.
The most common method of paracentral specification has been to describe the dose at a single reference point, usually one located 2 cm lateral to and 2 cm superior to the external cervical os in the plane of the intrauterine tandem (point A). Point A is a reference point developed as part of the Manchester system, which also incorporated a set of fairly rigid rules guiding application geometry and radioactive source loadings. Point A bears no consistent relation to tumor volume or target volume and has been localized in different ways by different investigators. However, dose specification for the purpose of treatment comparison should never be confused with dose prescription. Treatment should always be prescribed after careful consideration of information about the quality of the application, size of the applicator system, position of the system in the pelvis, exposure to normal tissue structures, initial tumor extent, and residual tumor, as well as the dose to tumor and normal tissue reference points.Treatment should also take into account the dose to lateral and more distant pelvic structures.
With ICRT, the dose to lateral structures is maximized when a relatively long tandem and large colpostats are used because a broader distribution of sources and greater displacement of the vagina permit more activity to be used without exceeding the maximum tolerable dose to bladder or rectum. A variety of reference points also have been used to estimate the dose to lateral pelvic structures. Point B (in the Manchester system) is usually located 3 cm lateral to point A, but its location in the pelvis varies considerably according to the position of the intracavitary system. Some clinicians also record the dose at a pelvic reference point P located just inside the lateral pelvic wall at the approximate level of the obturator lymph nodes.50 In the Fletcher system, bony landmarks are used to estimate the locations of the iliac lymph nodes (Fig. The external iliac nodes generally lie in a plane that intersects the tip of the pubic symphysis and the middle of S2.
The common iliac nodes lie along a plane between the anterior aspect of L4 and the bisector of the line between the pubis and S2.
However, CT-based three-dimensional analyses of the doses delivered to normal structures from ICRT demonstrate that standard reference points routinely underestimate the maximum dose delivered to these structures.51, 52 The artifact caused by standard intracavitary systems and other logistical concerns have made it difficult to perform routine three-dimensional analysis of treatment doses, but this is expected to be an active area of research in the next decade. Anteroposterior (A) and lateral cross-table (B) orthogonal radiographs of a patient with a normal findings on a lower-extremity lymphangiogram. The basic reference line is from the top of the symphysis to the junction of S1 and S2 (B). A line is drawn from the midpoint of the basic reference line to the middle of the anterior aspect of L4.
This was necessitated by practical considerations: the use of relatively low activity sources limited exposure of personnel to ionizing radiation during loading and unloading of the applicators and during nursing visits. However, laboratory and clinical studies also demonstrated that radiation therapy delivered at these low dose rates has an important radiologic advantage.53 The protracted continuous exposure has an effect similar to that of fractionated EBRT. The repair of sublethal injury in normal tissue cells exceeds that of tumor cells, maximizing the therapeutic ratio of ICRT.The development of computer-driven remote afterloading devices has made it possible to deliver brachytherapy with high activity sources with negligible exposure to personnel. Using these devices, radiation is delivered by advancing a single high-activity source along a track from the machine through the brachytherapy applicator.
The length of time the source rests in various positions determines the distribution of radiation dose.
This form of high-dose–rate brachytherapy is now used for a number of applications, including postoperative treatment of the vaginal apex, and in some practices, treatment of intact cervical cancers. However, because the dose-rate effect is lost, treatment must be divided into multiple fractions to achieve an acceptable ratio between the rates of tumor control and late radiation complications. Despite the possible radiobiologic concerns, high-dose–rate ICRT has a number of advantages. Although more applications are needed than with low-dose–rate treatment, the ability to give all treatment on an outpatient basis is frequently more convenient for patients and their physicians. Personnel exposure to ionizing radiation is virtually eliminated, and shielded inpatient hospital rooms are not required. For physicians who treat relatively few cases, capital costs may be less because the treatment can be delivered with the same high-dose–rate unit that is used for other purposes, eliminating the need to purchase cesium (which can be used only for cases of cervical or inoperable endometrial cancer). It has also been argued that the retraction methods used for high-dose–rate therapy, fixation of the applicator position during planning and treatment, and computerized optimization of source dwell positions may produce a more favorable ratio between the dose to tumor and normal tissues. For such patients, the maximum dose to normal tissues may be as high as or higher than the dose to tumor.
Although retrospective studies of patients treated for cervical cancer suggest that good survival rates can be achieved with high-dose–rate treatment, poor follow-up, small numbers of patients, and selection biases compromise many of these studies. In a small percentage of these cases, distal vaginal lesions may require treatment with a supplemental dose of radiation delivered using intralesional 192Ir interstitial implants.
With this technique, the dose to paracervical tissues is usually somewhat higher than that delivered with ICRT, but the central dose to the cervix is usually somewhat lower. A number of clinical trials have been completed or are underway, but at this time there is no proven benefit to combining chemotherapy with radiation”. Three years later, the first three6, 7, 8 of six large randomized trials investigating the role of concurrent cisplatin-based chemotherapy with radiation therapy were published in the New England Journal of Medicine.
The results were noted in a National Institutes of Health clinical alert and have significantly changed the standard of care for many patients with local-regionally advanced cervical cancer.A number of chemotherapeutic agents have modest activity against metastatic or recurrent carcinoma of the cervix.
Two of the GOG trials included concurrent hydroxyurea in their control arms, reflecting their earlier experiences with the drug.
The RTOG trial compared extended-field irradiation with a combination of pelvic irradiation, cisplatin, and 5-FU. Extended-field radiation therapy (including the pelvic and aortic nodes) had been found to be superior to pelvic irradiation in their earlier trial; extended-field radiation therapy was not used in their chemotherapy arm because of unacceptable toxicity observed with this combination in earlier phase II studies. A third GOG trial and the SWOG trial compared combinations of chemoradiation and hysterectomy with radiation therapy and surgery alone. The NCIC trial was a simple comparison of pelvic radiation therapy with or without concurrent cisplatin.
The eligibility criteria and treatment arms of these trials are outlined in Table 7.Table 7. Although the trials differed in their eligibility and control arms, all five demonstrated significantly better survival rates in their cisplatin-containing arms, with reductions in the risks of local recurrence, distant metastasis, and death of up to 50%. The authors of the NCIC trial argue that the less protracted radiation therapy regimen used for their patients may have been more effective, obviating chemotherapy. However, an examination of the outcome of their control arm suggests that there was a similar margin for improvement in local control and in other outcome measures. Wong and colleagues75 conducted a randomized trial of radiation therapy with or without concurrent and adjuvant epirubicin (an anthracycline unavailable in the United States). Progression-free survival was significantly better for patients who received chemotherapy (p = .03). In conjunction with Yale University, a group in Venezuela has been studying concurrent mitomycin C and 5-FU, a combination that has been highly successful in patients with anal cancer.
The authors have reported preliminary results that they considered to be encouraging, but the study is not yet mature and continues to accrue patients. In 1998, Thomas and colleagues76 reported the results of a four-arm trial that evaluated the role of concurrent continuous-infusion 5-FU (a successful regimen in patients with gastrointestinal adenocarcinomas).
This relatively small study did not show a significant improvement in survival with 5-FU, but the results were felt to be encouraging, particularly for the subset of patients with stage I and II disease.



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