Additional Notes

Cancer News
Chemotherapy and Other Agents
General Health Issues
Radiation Therapy
Study Reported by American Thyroid Association
Treatment

What are bone marrow and stem cells?

Where exactly are thyroid gland, larynx, and trachea located?

Cancer News

Chemotherapy and Other Agents

Sporadic experience indicates that bleomycin (544, 545), adriamycin (546), vinblastine (547), methotrexate (548), cisplatinum and other agents (549) may have value in treating disseminated thyroid tumors. Metastatic papillary or follicular tumors grow slowly and may respond completely (often temporarily) to 131I. Thus, chemotherapy is not indicated until the full value of 131I has been exploited, and then only when the tumor is clearly growing progressively despite hormone suppression. Treatment of MTC is generally reserved for definite symptomatic disease. Adriamycin is the most commonly used agent, but usually is used in combinations with other agents. Wu gave patients with metastatic MTC cyclophosphamide (750mg/m2), vinscristine (1.4mg/m2) and dacarbazine (600mg/m2 on 2 days), in cycles every 3 weeks, and found significant improvement and treatment was well tolerated. Lymphomas are often treated initially by chemothrapy. Undifferentiated lesions are given routine postoperative radiotherapy, and chemotherapy for recurrence or known spread. Prophylactic chemotherapy may soon be developed for these lesions. DeBesi et al. (550) found combined bleomycin, adriamycin, and platinum therapy in advanced cancer "probably" increased survival.

Intensive chemotherapy for anaplastic thyroid carcinoma using a combination of cisplatin, doxorubicin, etoposide, and peplomycin, and using granulocyte colony-stimulating factor for support of the bone marrow, was evaluated by the Japanese Society of Thyroid Surgery in a pilot investigation. Cisplatin, 40 mg/m2 intravenous infusion on day 1, plus adriamycin 60 mg/m2 iv on day 1, etoposide 100 mg/m2/day over days 1-3, peplomycin 5 mg/body/day sc on days 1-5, and granulocyte colony-stimulating factor, 2 m g/kg/day sc on days 6-14, was the program, and this was repeated every three weeks (Please review dosages in their publication). Some patients also received local radiation therapy. Several patients survived the anaplastic carcinoma for up to 11 months. This four drug regime did not achieve significant improvement over prior studies using other regimens. Because of the advanced age and the presence of high grade tumors, most patients received less than two cycles of therapy, which may have contributed to the unsatisfactory outcome (551). Paclitaxel has shown significant effects in treating anaplastic cancers but has not altered the lethality of the disease (552).  Combined chemotherapy and radiotherapy may also prolong survival significantly (553).

A very interesting new approach was recently reported by Santini et al. The slow growth of thyroid tumors has been considered a main reason for their resistance to conventional chemotherapy. These authors stimulated the tumors in 14 patients by either withdrawing a portion  of their replacement therapy or giving rhTSH, and then gave chemotherapy with carboplatinum plus epirubicin in six courses at 4-6 week intervals (554). One patient had a complete remission, five had partial remission, and seven had stabilization. While not cures, the results seem significantly better than usually achieved.

We offer for use the protocols developed by the Thyroid Cancer Treatment Cooperative Study Group (Table 18-12).

Table 18-12. Chemotherapy for Thyroid Carcinoma

1. Primary Tumor
        Progressive differentiated thyroid cancer, symptomatic medullary cancer, anaplastic cancer; two programs have been proposed
                    Adriamycin + cis-diamine-dichloroplatinum + Vp-16
                    Adriamycin + cis-diamine-dichloroplatinum

2. Secondary Therapy For Failure of Primary Treatment
                    Differentiated cancer -- bleomycin + cyclophosphamide
                    Medullary cancer -- 5-fluorouracil + streptozotocin
                    Anaplastic cancer -- bleomycin + hydroxyurea

ONYX-015 is an E1B deleted adenovirus that replicates in cells with impaired p53 function. p53 is commonly inactivated in anaplastic thyroid cancers. In vitro studies demonstrate that this virus induced cell death in in vitro trials in anaplastic cancer cell lines, and synergized with treatment with doxorubicin and pacitaxel (558).

NEW IDEAS-Possible alternative therapies for thyroid cancer, beyond surgery, RAI, and X-ray, are recently reviewed by Braga-Basaria and Ringel.  Methods under study include antisense compounds, phenylacetate and farnesyl transferase inhibitors targeting signaling pathways, antibodies against tyrosine kinase receptors, the immunosuppressive antibiotic rapamycin, demethylating agents, histone deacetylase inhibitors, and gene therapy.  Although none of these are of confirmed value, we are fortunate that a myriad of possible new therapies are on the horizon. Interestingly, lovastatin, used in the reduction of cholesterol therapeutically, induces apoptosis in human anaplastic thyroid carcinoma cells in vitro. Whether it has a beneficial effect in vivo remains unknown.

(http://www.thyroidmanager.org/Chapter18/18-chemothe.htm)

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Radiation Therapy

The general indications for radiation therapy are given in Table 18-11. Other sources should be reviewed for details of the port, dose, and methods of irradiation.

Radiotherapy was advised for treatment of anaplastic thyroid carcinoma, in an attempt to achieve local control, using hyperfractionation, possibly with the addition of doxorubicin. Radiotherapy was used for treatment of lymphomas, with a total dose of 35 – 40 Gy given over four weeks, and was typically preceded by the use of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every three to four weeks in three to six cycles prior to the radiotherapy. Cause-specific survival was 82% in patients who received combined therapy and 63% in those who got X-ray alone.

The exact dose must be individually determined, but usually the maximal dose is 5,000-6,000 rads, using ortho- or megavoltage, and a fractionated technique over several weeks. Dosage must be planned to assure that the spinal cord receives less than 3500 rads in order to avoid myelopathy.  

Table 18-11. Indications for Radiation Therapy

Tumor Stage     Treatment(15-20 MV Electrons or Co-60)
Papillary or Follicular Invasive, under age 50-55 Treat if invasive disease is thought not to be destroyed or if neck recurrence after 131-I. Dose is 4500-500 rads.
  Invasive or possible residual, over age 50-55 5000 rads* to thyroid bed after RAI
  Recurrent, any age 5000* rads to thyroid bed if RAI treatment is thought not to be definitive
  Isolated lesion in bone 5000-6000 rads, as required for symptoms after RAI treatment
Medullary Stage III 4000-5000* rads to thyroid bed
  Abnormal or increasing CT 5000* rads to mantle
  Recurrent tumor 5000-6000* rads to thyroid bed
  Isolated metastasis 5000-6000* rads for symptoms
Lymphoma Stage I-E, possibly II-E 5000 rads ** to thyroid and mantle
Anaplastic All 4500-5500 rads** to thyroid and mantle

(http://www.thyroidmanager.org/Chapter18/18-radiatio.htm)

 

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Study Reported by American Thyroid Association

Anaplastic cancer of the thyroid: a summary of 50 years' experience at a single institution

The background of the study. Approximately 2 percent of thyroid cancers are anaplastic.

How the study was done. The records of all patients with anaplastic thyroid cancer treated at the Mayo Clinic between 1949 and 1999 were reviewed. The diagnosis was confirmed in all patients by review of the original tissue sections.

The results of the study. There were 134 patients with anaplastic thyroid cancer during the 50-year interval, with no change in mean number per year during this period. Eighty (60 percent) were women and 54 (40 percent) were men; the mean age was 67 years. One hundred thirty patients (97 percent) presented with a rapidly enlarging neck mass (mean size, 7 cm). At diagnosis, most patients had positive lymph nodes in the neck, and 62 patients (46 percent) had distant metastases.

Treatment consisted of palliation only or biopsy followed by external radiation therapy or chemotherapy in 38 (28 percent). Ninety-six patients (72 percent) underwent surgery; it was intended to be curative in 35 patients (26 percent), was done to reduce the mass of tumor in 48 patients (36 percent), and was limited to biopsy in the remainder. Most patients received external radiation therapy after surgery, but only 1 patient had any decrease in tumor size.

(http://www.thyroid.org/patients/notes/march02/02_03_15.html)

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Treatment

Those rare patients who present with operable anaplastic thyroid carcinoma are usually discovered unexpectedly at frozen or permanent section. Most patients present with massive fixed tumors, which are unresectable. Those patients with unstable airway should be stabilized with endotracheal intubation if possible. Tracheotomy is often hazardous in this setting. Following biopsy, medical and radiation oncology consultations should be obtained.

Because anaplastic thyroid carcinoma is rare, large controlled studies of treatment are unavailable. Recent reports, suggest that combination treatment including accelerated radiation fractionation regimes, and radiosensitizing chemotherapy programs have improved local control. Some patients who have achieved a profound response to chemoradiotherapy seem to benefit from subsequent surgical resection.

Thyroidectomy following combined treatment can be considered if the patient remains free of distant metastases.

Chemotherapeutic agents which have been reported as effective include 5-FU, hydroxyurea, paclitaxel, and Adriamycin.

(http://www.headandneckcancer.org/clinicalresources/docs/anathyroid.php#TREATMENT)

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What are bone marrow and stem cells?

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells called stem cells that produce blood cells. There are three types of blood cells:

1. White blood cells, which fight infection.
2. Red blood cells, which carry oxygen to and remove waste products from organs and tissues.
3. Platelets, which enable the blood to clot.

Most stem cells are found in the bone marrow, but some stem cells called peripheral blood stem cells (PBSCs) can be found in the bloodstream. Umbilical cord blood also contains stem cells. Stem cells can divide to form more stem cells, or they can mature into white blood cells, red blood cells, or platelets.

To read the entire 1/24/03 Q&A article published by National Cancer Institute, click here.

(http://cis.nci.nih.gov/fact/7_41.htm)

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Where exactly are thyroid gland, larynx, and trachea located?

Graphical view of thyroid gland, larynx, and trachea.
The thyroid gland is located at the base of your neck, just below your Adam's apple.

Go back to top


Chemotherapy and Other Agents

Sporadic experience indicates that bleomycin (544, 545), adriamycin (546), vinblastine (547), methotrexate (548), cisplatinum and other agents (549) may have value in treating disseminated thyroid tumors. Metastatic papillary or follicular tumors grow slowly and may respond completely (often temporarily) to 131I. Thus, chemotherapy is not indicated until the full value of 131I has been exploited, and then only when the tumor is clearly growing progressively despite hormone suppression. Treatment of MTC is generally reserved for definite symptomatic disease. Adriamycin is the most commonly used agent, but usually is used in combinations with other agents. Wu gave patients with metastatic MTC cyclophosphamide (750mg/m2), vinscristine (1.4mg/m2) and dacarbazine (600mg/m2 on 2 days), in cycles every 3 weeks, and found significant improvement and treatment was well tolerated. Lymphomas are often treated initially by chemothrapy. Undifferentiated lesions are given routine postoperative radiotherapy, and chemotherapy for recurrence or known spread. Prophylactic chemotherapy may soon be developed for these lesions. DeBesi et al. (550) found combined bleomycin, adriamycin, and platinum therapy in advanced cancer "probably" increased survival.

Intensive chemotherapy for anaplastic thyroid carcinoma using a combination of cisplatin, doxorubicin, etoposide, and peplomycin, and using granulocyte colony-stimulating factor for support of the bone marrow, was evaluated by the Japanese Society of Thyroid Surgery in a pilot investigation. Cisplatin, 40 mg/m2 intravenous infusion on day 1, plus adriamycin 60 mg/m2 iv on day 1, etoposide 100 mg/m2/day over days 1-3, peplomycin 5 mg/body/day sc on days 1-5, and granulocyte colony-stimulating factor, 2 m g/kg/day sc on days 6-14, was the program, and this was repeated every three weeks (Please review dosages in their publication). Some patients also received local radiation therapy. Several patients survived the anaplastic carcinoma for up to 11 months. This four drug regime did not achieve significant improvement over prior studies using other regimens. Because of the advanced age and the presence of high grade tumors, most patients received less than two cycles of therapy, which may have contributed to the unsatisfactory outcome (551). Paclitaxel has shown significant effects in treating anaplastic cancers but has not altered the lethality of the disease (552).  Combined chemotherapy and radiotherapy may also prolong survival significantly (553).

A very interesting new approach was recently reported by Santini et al. The slow growth of thyroid tumors has been considered a main reason for their resistance to conventional chemotherapy. These authors stimulated the tumors in 14 patients by either withdrawing a portion  of their replacement therapy or giving rhTSH, and then gave chemotherapy with carboplatinum plus epirubicin in six courses at 4-6 week intervals (554). One patient had a complete remission, five had partial remission, and seven had stabilization. While not cures, the results seem significantly better than usually achieved.

We offer for use the protocols developed by the Thyroid Cancer Treatment Cooperative Study Group (Table 18-12).

Table 18-12. Chemotherapy for Thyroid Carcinoma

1. Primary Tumor
        Progressive differentiated thyroid cancer, symptomatic medullary cancer, anaplastic cancer; two programs have been proposed
                    Adriamycin + cis-diamine-dichloroplatinum + Vp-16
                    Adriamycin + cis-diamine-dichloroplatinum

2. Secondary Therapy For Failure of Primary Treatment
                    Differentiated cancer -- bleomycin + cyclophosphamide
                    Medullary cancer -- 5-fluorouracil + streptozotocin
                    Anaplastic cancer -- bleomycin + hydroxyurea

ONYX-015 is an E1B deleted adenovirus that replicates in cells with impaired p53 function. p53 is commonly inactivated in anaplastic thyroid cancers. In vitro studies demonstrate that this virus induced cell death in in vitro trials in anaplastic cancer cell lines, and synergized with treatment with doxorubicin and pacitaxel (558).

NEW IDEAS-Possible alternative therapies for thyroid cancer, beyond surgery, RAI, and X-ray, are recently reviewed by Braga-Basaria and Ringel.  Methods under study include antisense compounds, phenylacetate and farnesyl transferase inhibitors targeting signaling pathways, antibodies against tyrosine kinase receptors, the immunosuppressive antibiotic rapamycin, demethylating agents, histone deacetylase inhibitors, and gene therapy.  Although none of these are of confirmed value, we are fortunate that a myriad of possible new therapies are on the horizon. Interestingly, lovastatin, used in the reduction of cholesterol therapeutically, induces apoptosis in human anaplastic thyroid carcinoma cells in vitro. Whether it has a beneficial effect in vivo remains unknown.

(http://www.thyroidmanager.org/Chapter18/18-chemothe.htm)

Go back to top


Radiation Therapy

The general indications for radiation therapy are given in Table 18-11. Other sources should be reviewed for details of the port, dose, and methods of irradiation.

Radiotherapy was advised for treatment of anaplastic thyroid carcinoma, in an attempt to achieve local control, using hyperfractionation, possibly with the addition of doxorubicin. Radiotherapy was used for treatment of lymphomas, with a total dose of 35 – 40 Gy given over four weeks, and was typically preceded by the use of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every three to four weeks in three to six cycles prior to the radiotherapy. Cause-specific survival was 82% in patients who received combined therapy and 63% in those who got X-ray alone.

The exact dose must be individually determined, but usually the maximal dose is 5,000-6,000 rads, using ortho- or megavoltage, and a fractionated technique over several weeks. Dosage must be planned to assure that the spinal cord receives less than 3500 rads in order to avoid myelopathy.                                           

Table 18-11. Indications for Radiation Therapy

Tumor Stage     Treatment(15-20 MV Electrons or Co-60)
Papillary or Follicular Invasive, under age 50-55 Treat if invasive disease is thought not to be destroyed or if neck recurrence after 131-I. Dose is 4500-500 rads.
  Invasive or possible residual, over age 50-55 5000 rads* to thyroid bed after RAI
  Recurrent, any age 5000* rads to thyroid bed if RAI treatment is thought not to be definitive
  Isolated lesion in bone 5000-6000 rads, as required for symptoms after RAI treatment
Medullary Stage III 4000-5000* rads to thyroid bed
  Abnormal or increasing CT 5000* rads to mantle
  Recurrent tumor 5000-6000* rads to thyroid bed
  Isolated metastasis 5000-6000* rads for symptoms
Lymphoma Stage I-E, possibly II-E 5000 rads ** to thyroid and mantle
Anaplastic All 4500-5500 rads** to thyroid and mantle

(http://www.thyroidmanager.org/Chapter18/18-radiatio.htm)

Go back to top


Study Reported by American Thyroid Association

Anaplastic cancer of the thyroid: a summary of 50 years' experience at a single institution

The background of the study. Approximately 2 percent of thyroid cancers are anaplastic.

How the study was done. The records of all patients with anaplastic thyroid cancer treated at the Mayo Clinic between 1949 and 1999 were reviewed. The diagnosis was confirmed in all patients by review of the original tissue sections.

The results of the study. There were 134 patients with anaplastic thyroid cancer during the 50-year interval, with no change in mean number per year during this period. Eighty (60 percent) were women and 54 (40 percent) were men; the mean age was 67 years. One hundred thirty patients (97 percent) presented with a rapidly enlarging neck mass (mean size, 7 cm). At diagnosis, most patients had positive lymph nodes in the neck, and 62 patients (46 percent) had distant metastases.

Treatment consisted of palliation only or biopsy followed by external radiation therapy or chemotherapy in 38 (28 percent). Ninety-six patients (72 percent) underwent surgery; it was intended to be curative in 35 patients (26 percent), was done to reduce the mass of tumor in 48 patients (36 percent), and was limited to biopsy in the remainder. Most patients received external radiation therapy after surgery, but only 1 patient had any decrease in tumor size.

(http://www.thyroid.org/patients/notes/march02/02_03_15.html)

Go back to top


Treatment

Those rare patients who present with operable anaplastic thyroid carcinoma are usually discovered unexpectedly at frozen or permanent section. Most patients present with massive fixed tumors, which are unresectable. Those patients with unstable airway should be stabilized with endotracheal intubation if possible. Tracheotomy is often hazardous in this setting. Following biopsy, medical and radiation oncology consultations should be obtained.

Because anaplastic thyroid carcinoma is rare, large controlled studies of treatment are unavailable. Recent reports, suggest that combination treatment including accelerated radiation fractionation regimes, and radiosensitizing chemotherapy programs have improved local control. Some patients who have achieved a profound response to chemoradiotherapy seem to benefit from subsequent surgical resection.

Thyroidectomy following combined treatment can be considered if the patient remains free of distant metastases.

Chemotherapeutic agents which have been reported as effective include 5-FU, hydroxyurea, paclitaxel, and Adriamycin.

(http://www.headandneckcancer.org/clinicalresources/docs/anathyroid.php#TREATMENT)

Go back to top


What are bone marrow and stem cells?

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells called stem cells that produce blood cells. There are three types of blood cells:

1. White blood cells, which fight infection.
2. Red blood cells, which carry oxygen to and remove waste products from organs and tissues.
3. Platelets, which enable the blood to clot.

Most stem cells are found in the bone marrow, but some stem cells called peripheral blood stem cells (PBSCs) can be found in the bloodstream. Umbilical cord blood also contains stem cells. Stem cells can divide to form more stem cells, or they can mature into white blood cells, red blood cells, or platelets.

To read the entire 1/24/03 Q&A article published by National Cancer Institute, click here.

(http://cis.nci.nih.gov/fact/7_41.htm)

Go back to top


Where exactly are thyroid gland, larynx, and trachea located?

Graphical view of thyroid gland, larynx, and trachea.
The thyroid gland is located at the base of your neck, just below your Adam's apple.

Go back to top



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