Saturday, February 17, 2024

Chemo For Endometrial Cancer Success

If The Cancer Comes Back

Endometrial Cancer Treatment: Surgery & Personalized Medicine – Joshua Cohen, MD | UCLAMDChat

If cancer does come back at some point, your treatment options will depend on where the cancer is, what treatments youâve had before, and your health. Surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, or some combination of these might be options. Other types of treatment might also be used to help relieve any symptoms from the cancer.

For more on how recurrent cancer is treated, see Treatment Choices of Endometrial Cancer, by Stage. For more general information see Understanding Recurrence.

Early Chemo Does Not Improve Survival In Endometrial Cancer

Endometrial cancer survival correlates with total number of chemotherapy cycles but not whether they are started earlier than radiation, according to the results of a new study.

Endometrial cancer survival correlates with total number of chemotherapy cycles but not whether they are started earlier than radiation, according to the results of a new study.

The overall survival and cancer-specific survival rates were not improved by receiving early chemo, defined as adjuvant chemotherapy before adjuvant radiation therapy, either with or without additional chemo sandwich regimens, according to the study in the American Journal of Clinical Oncology.

No differences in OS or CSS were noted among endometrial patients receiving early chemotherapy, concluded the authors, from the Huntsman Cancer Institute at the University of Utah. However, the number of chemotherapy cycles was associated with prolonged survival.

Patients that received both chemo and radiation for their endometrial cancer were selected from the SEER-Medicare database 597 were selected. The median age was 72 years, and 85% of the patients were white.

Sixty-eight percent of the women had stage III disease, as defined by the International Federation of Gynecology and Obstetrics . Some 77% of the patients received between 4 and 6 cycles of chemotherapy, with the remainder having either 1 to 3 cycles, or 7 or more.

Treatment Options Under Clinical Evaluation For Stage I And Stage Ii Endometrial Cancer

  • The GOG-0249 trial compared the combination of adjuvant carboplatin and paclitaxel and vaginal cuff brachytherapy versus adjuvant pelvic EBRT in high-risk endometrial cancer patients with stage I or II disease. The study is closed to accrual, and preliminary findings have been presented in abstract form, showing no significant difference between the two treatment arms.
  • The GOG-0261 trial compared paclitaxel and carboplatin with paclitaxel and ifosfamide in patients with newly diagnosed stages I to IV persistent or recurrent uterine, ovarian, fallopian tube, or peritoneal cavity cancer.
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    What Is The Evidence For Specific Management And Treatment Recommendations

    Fung-Kee-Fung, M, Dodge, J, Elit, L. âFollow-up after primary therapy for endometrial cancer: a systematic reviewâ. Gynecol Oncol. vol. 101. 2006. pp. 520-9.

    Aalders, JG, Abeler, V, Kolstad, P. âRecurrent adenocarcinoma of the endometrium: a clinical and histopathological study of 379 patientsâ. Gynecol Oncol. vol. 17. 1984. pp. 85

    Haie-Meder, C, Mazeron, R, Magne, N. âClinical evidence on PET-CT for radiation therapy planning in cervix and endometrial cancersâ. Radiother Oncol. vol. 96. 2010. pp. 351-5.

    Fiorica, JV, Brunetto, VL, Hanjani, P. âPhase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group studyâ. Gynecol Oncol. vol. 92. 2004. pp. 10-4.

    Fleming, GF, Brunetto, VL, Cella, D. âPhase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group studyâ. J Clin Oncol. vol. 22. 2004. pp. 2159-66.

    Du Bois, A, Pfisterer, J, Burchardi, N. âCombination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: a prospective phase II study of the Arbeirsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom and Kommission Uterus â. Gynecol Oncol. vol. 107. 2007. pp. 518-25.

    Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.

    Doctor Visits And Tests

    Endometrial Cancer: Symptoms, Causes and Treatment â Healthsoul

    Endometrial cancer is most likely to come back within the first few years after treatment, so an important part of your treatment plan is a specific schedule of follow-up visits after treatment ends. How often you need to be seen depends mostly on what stage and grade the cancer was.

    • For most women who had endometrial cancer, experts recommend a physical exam every 3 to 6 months for the first 2 to 3 years, then every 6 or 12 months after that. Imaging tests should be done based on the physical exam and any changes the patient reports.
    • For women with higher stage or grade cancers , experts recommend that, along with physical exams, a CT scan of the chest, abdomen , and pelvis is done every 6 months for the first 3 years, then every 6 to 12 months for at least the next 2 years.

    If symptoms or the physical exam suggests the cancer might have come back, imaging tests , a CA 125 blood test, and/or biopsies may be done. Studies of many women with endometrial cancer show that if no symptoms or physical exam changes are present, routine blood tests and imaging tests aren’t needed.

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    Future Directions In Adjuvant Therapy

    Although there have been randomized trials comparing radiotherapy with chemoradiotherapy, there are not yet prospective data comparing adjuvant chemotherapy alone with radiation therapy plus chemotherapy. GOG 258, which completed accrual in July 2014, randomized patients with stage III or IVA endometrial carcinoma to either volume-directed radiation therapy with two doses of concomitant cisplatin followed by four cycles of carboplatin/paclitaxel, or six cycles of carboplatin/paclitaxel with no radiotherapy. Accrual is complete, and final analysis is expected in 2016.

    Another trial asking a similar question regarding the benefit of adding radiotherapy to chemotherapy, but in earlier-stage disease, is the Danish Gynaecological Cancer Group -EN2 adjuvant study, which tests brachytherapy alone versus brachytherapy plus six cycles of carboplatin/paclitaxel chemotherapy in node-negative, stage III intermediate or high-risk endometrial cancer. Accrual is ongoing.

    Side Effects Of Chemotherapy

    These drugs kill cancer cells but can also damage some normal cells, which in turn causes side effects. Side effects of chemotherapy depend on the drugs used, the amount taken, and how long treatment is given. Common side effects include:

    • Nausea and vomiting

    Also, most chemo drugs can damage the blood-producing cells of the bone marrow. This can result in low blood cell counts, such as:

    • Low white blood cells, which increases the risk of infection
    • Low platelet counts, which can cause bleeding or bruising after minor cuts or injuries
    • Low red blood cells , which can cause problems like fatigue and shortness of breath

    Most of the side effects of chemotherapy get better over time when treatment ends, but some can last a long time. Different drugs can cause different side effects. For instance, doxorubicin can damage the heart muscle over time. The chance of heart damage goes up as the total dose of the drug goes up, so doctors put a limit on how much doxorubicin a person can get.

    Cisplatin can cause kidney damage, so you’ll be given lots of IV fluids before and after chemo to help protect the kidneys. Both cisplatin and paclitaxel can cause nerve damage . This can lead to numbness, tingling, or even pain in the hands and feet. Ifosfamide can injure the lining of the bladder, causing it to bleed . To prevent this, you might be given large amounts of IV fluids and a drug called mesna along with the chemo.

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    Treatment Of Stage Iii Stage Iv And Recurrent Endometrial Cancer

    In This Section

    Treatment of patients with stage IV endometrial cancer is dictated by the site of metastatic disease and symptoms related to disease sites.

    Surgery followed by chemotherapy or radiation therapy

    In general, patients with stage III or stage IV endometrial cancer are treated with surgery, followed by chemotherapy or radiation therapy, or both.Observational studies support maximal cytoreductive surgery for patients with stage IV disease, although these conclusions need to be interpreted with care because of the small number of cases and likely selection bias.

    For many years, radiation therapy was the standard adjuvant treatment for patients with endometrial cancer. However, several randomized trials have confirmed improved survival when adjuvant chemotherapy is used instead of radiation therapy.

    Doxorubicin was historically the most active anticancer agent employed,with useful but temporary responses obtained in as many as 33% of patientswith recurrent disease. Paclitaxel, in combination with platinum chemotherapy or as a single agent, also has significant anticancer activity.

    Evidence :

  • Several randomized trials by the Gynecologic Oncology Group have utilized the known antitumor activity of doxorubicin.
  • The addition of cisplatin to doxorubicin increased response rates and progression-free survival above those of doxorubicin alone but without an effect on overall survival .
  • Chemotherapy and radiation therapy

    Hormone therapy

    • Hydroxyprogesterone.

    Biologic therapy

    Stage 1 Uterine Cancer

    Endometrial cancer – causes, symptoms, diagnosis, treatment, pathology

    Cancer doesnt go outside the uterus at this stage. It also affects the cervix glands, a thin channel at the uterus bottom.

    Stage 1A: Cancer moves to the endometrium, the uteruss inner lining. It is possible that it went only halfway into the muscle beneath.

    Stage 1B: The malignancy moves across the endometrium and up to half of the core muscle affecting the uterine cancer stage 1 survival rate.

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    Infiltration Of Immune Cell Subsets In Different Molecular Subtypes Of Ec

    We examined tumor-infiltrating immune cells in the three molecular subtypes using multiplex immunofluorescence assays . The fractions of CD8+ T cells in both the tumor parenchyma and the tumor mesenchyme were higher in the TMB-H and TP53 mutant subtypes than in the NSMP subtype, although the differences were not statistically significant . The infiltration of M1 macrophages and CD56dim NK cells did not differ significantly among the three subtypes.

    Figure 3 Immune infiltration in different molecular subtypes of EC by multiplex immunofluorescence. The immune infiltrations in EC of POLE mutant subtype. Intense red fluorescence indicates large amount of CD8+ cell infiltration. The immune infiltration in EC of MSI-H subtype. The immune infiltration in NSMP subtype. Few fluorescence signals could be observed, indicating absence of immune infiltration. The immune infiltration in TP53 mutant subtype. Intense yellow fluorescence indicates the infiltration of FOXP3+ cells. For each subtype, a representative filed was selected, and the major tumor regions are outlined. TMB-H, high tumor mutation burden MSI-H, microsatellite instability high NSMP, no specific molecular profile EC, endometrial cancer.

    What Are The Survival Rates For Endometrial Cancer

    How well treatment works for women with endometrial cancer depends on the type and stage of cancer. Below are the 5-year relative survival rates based on the stage of the endometrial cancer when it was diagnosed. A 5-year survival rate means how many women are alive 5 years after diagnosis. Relative survival rates take into account that some women will die of other causes and compare the observed survival with that expected for women who dont have endometrial cancer.

    The 5-year relative survival rates are:

    • 90% for women with stage 0

    • 88% for women with stage IA

    • 75% for women with stage IB

    • 69% for women with stage II

    • 58% for women with stage IIIA

    • 50% for women with stage IIIB

    • 47% for women with stage IIIC

    • 17% for women with stage IVA

    • 15% for women with stage IVB

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    Pathogenesis And Molecular Biology

    Microscopically, uterine serous carcinomas have a predominate papillary pattern and can also have more solid areas with slit-like glandular spaces . Up to one-third of cases can be of mixed histology with varying amounts of endometrioid or clear cell carcinoma. Pathologists are often confronted with the need to classify these tumors despite seemingly divergent microscopic findings. Immunohistochemical stains are frequently used to further categorize tumors when histology alone is unclear. One of the often-cited features of uterine serous carcinoma on immnunohistochemistry is abnormal p53 staining. Although p53 staining, especially the pattern compatible with missense TP53 mutations, is a useful marker to support the diagnosis of uterine serous carcinoma. Notably, high-grade endometrioid carcinoma and high-grade serous carcinomas of the fallopian tube and ovary also show the same staining pattern. Diffuse p16 and minimum WT-1 immunostaining are also frequently used in pathology as adjuncts to assist the differential diagnosis in difficult cases.

    Gross and microscopic features of uterine serous carcinoma. The 7cm tumor mass occupies the posterior uterine cavity. . Histology shows the characteristic papillary architecture with highly atypical tumor cells. . A high-magnification view reveals invasion of the tumor into a blood vessel. The carcinoma cells are high grade and an abnormal mitotic figure is evident.

    Living As An Endometrial Cancer Survivor

    High

    For many women with endometrial cancer, treatment may remove or destroy the cancer. Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about cancer coming back. This is a very common concern in people who have had cancer.

    For other women, this cancer may never go away completely. They may get regular treatments with chemotherapy, radiation, or other therapies to try to help keep the cancer in check. Learning to live with cancer that doesn’t go away can be difficult and very stressful.

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    Ask Your Doctor For A Survivorship Care Plan

    Talk with your doctor about developing a survivorship care plan for you. This plan might include:

    • A suggested schedule for follow-up exams and tests
    • A list of potential late or long-term side effects from your treatment, including what to watch for and when you should contact your doctor
    • A schedule for other tests you might need, such as tests to look for long-term health effects from your cancer or its treatment
    • Suggestions for things you can do that might improve your health, including possibly lowering your chances of the cancer coming back

    Stage I Endometrioid Cancers

    Standard treatment includes surgery to remove and stage the cancer . Sometimes this is the only treatment needed. The patient is then closely watched for signs that the cancer has come back .

    For women with higher grade tumors, radiation will likely be recommended after surgery. Vaginal brachytherapy , pelvic radiation, or both can be used.

    Some younger women with early endometrial cancer may have their uterus removed without removing the ovaries. This prevents menopause and the issues that can come with it. This also increases the chance that the cancer will come back, but it doesnt make it more likely that you will die from the cancer. This may be something that you want to discuss with your doctor.

    Women who cannot have surgery because of other medical problems or who are frail due to age are often treated with just radiation .

    Many times, progestin treatment doesn’t work and the cancer doesnt get better or keeps growing. Putting off surgery can give the cancer time to spread outside the uterus. If it doesnt go away in 6 to 12 months , surgery to remove and stage the cancer is recommended .

    A second opinion from a gynecologic oncologist and pathologist before starting progestin therapy is important. Seeing a fertility expert is also a good idea. It’s important to understand that this isn’t a standard treatment and may increase risk of cancer growth and spread.

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    B What Should The Initial Definitive Therapy For The Cancer Be

    Initial therapy for recurrent endometrial carcinoma is dependent on features such as number and location of metastatic deposits, tumor grade, and presence of progesterone receptor expression. Isolated vaginal recurrences or nodal recurrences in a non-irradiated field may be treated with radiation therapy with curative intent, while vaginal recurrences in a previously radiated field and solitary distant metastases, such a lung nodule, may occasionally be amenable to surgical resection with a possibility of cure.

    Whether chemotherapy should be added to radiation in the treatment of vaginal/pelvic recurrences is not clear. There is currently an ongoing randomized clinical trial, GOG 238, testing pelvic irradiation with our without concomitant weekly cisplatin in patients with pelvic-only recurrence of endometrial carcinoma.

    More extensive recurrence and multiple distant metastases are treated with hormonal therapy or cytotoxic chemotherapy. Progestins, such as megestrol acetate, are the mainstay of hormonal therapy. Overall response rates are modest the highest response rates are seen in women whose tumors are low grade and progesterone receptor positive, who have a small volume of tumor, and have had a protracted disease-free interval.

    • Paclitaxel 175 mg/m 2 + carboplatin AUC 5-6 every 3 weeks .

    • PLD 40 mg/m 2 + carboplatin AUC 5 every 4 weeks

    • Zoledronic acid 4 mg intravenously every 3-4 weeks .

    • Denosumab 120 mg subcutaneously every 4 weeks .

    Types Of Endometrial Cancer

    Cancer – Endometrial, Cervical, Ovarian & Breast Cancer: Medical-Surgical | @Level Up RN

    Uterine carcinosarcomas, a poorly differentiated subgroup of uterine carcinomas, account for less than 5% of all uterine malignancies and are rare, aggressive biphasic neoplasms that consist of high-grade malignant epithelial and mesenchymal elements . Five-year progression-free survival rates for uterine-confined disease range from 40 to 75%, compared with 2035% for disease with extra-uterine extension .

    The Cancer Genome Atlas Research Network has performed the most comprehensive molecular study of EC, integrating genomic, transcriptomic, and proteomic characterizations of EC based on array and sequencing technologies in 373 primary EC surgical specimens . These data revealed that EC can be classified into four molecularly phenotypically different groups: 1) DNA polymerase epsilon catalytic subunit ultramutated 2) MSI hypermutated 3) copy-number low , endometrioid histology, grade 1/2 tumors, and characterized by mutations in PTEN , CTNNB1 , PIK3CA , PIK3R1 , and ARID1A ) and 4) copy-number high serous-like .

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    Survival For All Stages Of Womb Cancer

    Generally for women with womb cancer in England:

    • 90 out of every 100 survive their cancer for 1 year or more after they are diagnosed
    • around 75 out of every 100 will survive their cancer for 5 years or more
    • more than 70 out of every 100 will survive their cancer for 10 years or more after diagnosis

    Cancer survival by stage at diagnosis for England, 2019Office for National Statistics

    These figures are for people diagnosed in England between 2013 and 2017.

    These statistics are for net survival. Net survival estimates the number of people who survive their cancer rather than calculating the number of people diagnosed with cancer who are still alive. In other words, it is the survival of cancer patients after taking into account that some people would have died from other causes if they had not had cancer.

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