I decided to open this new forum ti highlight that there is a new information that provide a hint that IFN-alpha might be of interest to consider for the microscopic disease and I invite everyone who has more info (personal or anecdotal or published) post here. We had people using IFN alpha unsuccessfully for the advanced metastatic disease though.
The new info we received was a recent (January 2013) update from the curesearch re. status of their daughter http://www.cureasps.org/forum/viewtopic ... 7&start=15
"
Update: 10 years after ASPS diagnosis
Postby cureSearch » Sat Jan 12, 2013 11:52 am
Hello everyone,
Our daughter was diagnosed with ASPS in the summer of 2003, almost 10 years ago. Between 2003 to 2007, she went through 3 surgeries to remove the primary tumor and all large tumors above 3mm in both her lungs. Since 2007 there are no growing tumors in her body.
Recently in a lung CT scan we learned very exciting news, that there are indications that small met-lungs seen since 2003 are shrinking.
Those findings are very encouraging and I hope that they will help others to make decisions regarding treatment of their loved once: It is important to perform radical surgeries to remove all the ASPS tumors from the body. Treatment with Interferon alpha 2b may help. Here is a summary of everything that our daughter has done in the last 10 years:
1. Shortly after the diagnosis in September 2003 she started an interferon alpha 2b treatment of 5 MIU (million units) daily. This dose was reduced in October 2004 to 3 MIU and continued for the total of 13 months.
2. In September 2003 she had surgery to remove her primary tumor from the shoulder.
3. In February 2005 our daughter went on a surgery to remove more than fifteen tumors larger then 3mm in her right lung.
4. In February 2007 our daughter went on a surgery to remove one growing met in her left lung and additional tumors larger than 3 mm.
5. Since February 2007 we learned that all the small remaining lung mets do not change their size and in December 2012 we learned that it is possible that remaining mets are shrinking.
Best Wishes to all of you.
"
that I decided to copy here as it goes well with the other (although rare) single case reports when IFN was used with the similar result.
These are the links to the resorts published on the Pubmed:
1. Free full text:
Alveolar soft-part sarcoma responding to interferon alpha-2b.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394261/
2. No free text/no abstract:
2.1. Alveolar soft part sarcoma with lung metastases. Response to interferon alpha-2a?
http://www.ncbi.nlm.nih.gov/pubmed/11745882
2.2. Interferon alpha for alveolar soft part sarcoma.
http://www.ncbi.nlm.nih.gov/pubmed/15602705
Why is it open
Why is it open
Olga
Re: Why is it open
Here is the full text of 2.1. and 2.2. It doesn't add that much, but I thought it might be helpful having the details.
2.1.
Alveolar soft part sarcoma with lung metastases. Response to interferon alpha-2a?
Kuriyama K, Todo S, Hibi S, Morimoto A, Imashuku S.
Med Pediatr Oncol. 2001 Nov;37(5):482-3.
To the Editor: We read with interest the report by
Pappo et al. entitled ``Alveolar soft part sarcoma in
children and adolescents: clinical features and outcome
of 11 patients'' [1]. Our experience with a boy with
alveolar soft part sarcoma (ASPS) with lung metastases is
relevant. The patient has remained in good health despite
persistence of lung metastases over 9 years from the
initial diagnosis and 6 years after discontinuation of
chemo-cytokine therapy. Review of the course of his
disease suggests a previously unknown susceptibility of
ASPS to treatment with interferon alpha (INF-a).
A previously healthy 8-year-old boy presented without
pain with an approximately 4-cm tumor on the upper and
interior side of his left knee on 5 February 1991. The
tumor was grossly resected and its histologic assessment
led to a diagnosis of ASPS. Macroscopic ®ndings at
surgery indicated that the tumor was not well circumscribed
and had invaded into the surrounding vastus
medialis muscle. At the time of diagnosis, chest radiography
and computed tomography (CT) scanning also
revealed multiple pulmonary metastases. The patient was
referred to the Kyoto Prefectural University of Medicine
for postoperative chemotherapy. His treatment consisted
of combinations of vincristine(VCR)/doxorubicin(ADR)/
cyclophosphamide(CPM), etoposide/cisplastin, CPM/
VCR/dactinomycin (Act-D), and ADR/VCR/ifosfamide.
This was followed by maintenance therapy consisting of
VCR, Act-D, and CPM for nine months between March
1991 and December 1991. The number and size of the
lung metastases remained stable throughout the course of
chemotherapy; after discontinuation of treatment, however,
the lung metastases gradually grew in size and
number. Consequently, in December 1992, the patient
was treated with INF-a -2a (3 million IU, i.m. three times
per week). After 6 months of interferon therapy (total
doses 216 million IU), the number of lung metastases had
decreased slightly, indicating a partial response (Fig. 1A).
At this point, however, the patient and his parents refused
to continue the treatment and the patient was lost to
follow-up age eleven.
On 25 February 2000, at 17 years of age, the patient
presented with chest pain to another hospital where
multiple lung nodules were seen on chest X-ray ®lms and
CT scans. Given his past history of ASPS, he was referred
to our hospital on 1 March 2000. We established there
was no recurrence at the primary site and that the patient
had been in good condition (Karnofsky score of 100%)
during the intervening years without receiving any
treatment. His complaint of chest pain was not related
to the original disease. When the present and past lung
CT scans were compared, we observed that his lung
metastases had decreased in number and diameter.
(Fig. 1B). His respiratory function was also found to be
within normal limits (100.0% vital capacity, 104.3%
forced expiratory volume1.0). As the patient had a good
quality of life, no organ dysfunction, and did not wish to
be treated, we decided to withhold further therapy but to
maintain close long-term surveillance.
Information on the precise long-term course to be
expected in a case such as ours is limited. (2,3) Our
survey of the literature revealed only three cases of ASPS
with lung metastases surviving longer than 3 years at
the time of those reports. These data must be coupled
with the fact the nodules in our patient grew after chemotherapy
and decreased in size only after the initiation
of INF-a-2a. Spontaneous remission of disease seems
a less likely explanation than ascribing the changes to
INF-a-2a.
The possible efficacy of INF-a-2a in treating ASPS
has not been previously reported, although experimental
studies have shown that INF-a is effective in treating
soft tissue sarcomas in general [4,5]. INF-a was found to
inhibit their in vitro proliferation in a manner that is
independent of their p53 status, although it did not induce
apoptosis in a soft tissue sarcoma cell line [4]. In
addition, Rosolen et al. [5] have shown that all solid
tumors that develop during childhood express INF-a
type 1 receptors and that treatment of these tumors with
INF-a inhibits their in vitro growth. Given these data on
the in vitro efficacy of INF-a, we speculate that the ASPS
in our patient may have responded to and been stabilized
by INF-a-2a, accounting for his long-term partial
remission without disease exacerbation. It is thus of
interest to know if ASPS expresses the INF-a receptor.
Despite its characteristic histologic features, ASPS remains
a tumor of controversial histogenesis and unclear
pathogenesis. In the past, immunohistochemical studies
have suggested that it may be both of neural and muscle
origin [2,3], and recent reports have confirmed its neural
origin by molecular and cytogenetic analyses [6]. Rosolen
et al. [5] have shown that neuro-endocrine tumors that
develop in childhood (i.e., neuroblastomas and primitive
neuroectodermal tumors) express the INF-a receptor and
are susceptible to the anti-proliferative effects of INF-a.
Further studies are necessary to con®rm the effectiveness
of INF-a in treating ASPS and to assess how this might be
related to the biologic characteristics and histogenesis of
ASPS.
Kikuko Kuriyama, MD*
Shinjiro Todo, MD
Shigeyoshi Hibi, MD
Akira Morimoto, MD
Department of Pediatrics
Kyoto Prefectural University of Medicine
Kyoto, Japan
Shinsaku Imashuku, MD
Kyoto City Institute of Health and
Environmental Sciences
Kyoto, Japan
REFERENCES
1. Pappo AS, Parham DM, Cain A, et al. Alveolar soft part sarcoma in
children and adolescents: clinical features and outcome of
11 patients. Med Pediatr Oncol 1996;26:81±84.
2. Ordonez NG. Alveolar soft part sarcoma: A review and update.
Adv Anat Pathol 1999;6:125±139.
3. Enzinger FM, Weiss SW. Alveolar soft part sarcoma. Soft Tissue
Tumors, 3rd Ed. St. Louis, 1995. P 13, and 1067±1074.
4. Brodowicz T, Wiltschke C, Kandioler-Eckersberger D. et al.
Inhibition of proliferation and induction of apoptosis in soft tissue
sarcoma cells by interferon-alpha and retinoids. Br J Cancer
1999;80:1350±1358.
5. Rosolen A, Todesco A, Colamonici OR et al. Expression of type I
interferon receptor in solid tumors of childhood. Mod Pathol
1997;10:55±61.
6. Chan AS, Squire JA, Thorner P et al. Molecular genetic changes in
alveolar soft part sarcoma. Pediatr Pathol Molecul Med 2000;18:
529±543.
2.2.
Interferon alpha for alveolar soft part sarcoma
Gianni Bisogno, Rosolen A, Carli M.
Pediatric Blood & Cancer
Volume 44, Issue 7, pages 687–688, 15 June 2005
To the Editor: Alveolar soft-part sarcoma (ASPS) is a rare malignant tumor for whom chemotherapy has little or no efficacy. Although we reported on some patients responding to conventional chemotherapy, results were ultimately disappointing if the tumor was not completely resected 1. Thus, new approaches are needed for patients with unresectable ASPS. The possible activity of interferon alpha (IFN) against ASPS has been previously documented 2. More recently Roozendaal et al. 3 described a partial remission induced by IFN 2b in a patient with ASPS. We therefore decided to use IFN in a patient with a chemoresistant ASPS.
A 7-year old girl presented in September 1996 with a rapidly-growing mass in her right buttock. A biopsy was performed confirming the diagnosis of ASPS. Staging revealed multiple lung metastases. Chemotherapy was administered according to the European MMT4 protocol without benefit. Further chemotherapy with topotecan and cyclophosphamide achieved no improvement and a very slow increase in the number and size of the pulmonary lesions was demonstrated on CT scan. Because the patient was otherwise in very good general condition, in March 1997 we agreed with the family to stop any further treatment, apart from irradiating the buttock lesion to diminish the local discomfort.
Towards the end of 2003, the patient's general condition suddenly deteriorated, with rapid weight loss (from 45 to 37 kg in approximately 1 month) and increasing respiratory insufficiency (oxygen saturation in the range of 91%–93%). New imaging studies showed an increase in the metastatic lesions (Fig. 1a) and revealed an intracerebral mass in the frontal lobe. With the family's and patient's consent, treatment with IFN 2b (3 × 106 IU s.c. day) was initiated. During the treatment, she suffered further weight loss and fever. Oral steroids (prednisone 25 mg daily) were given to ameliorate the symptoms. The fever disappeared and food intake improved. IFN treatment was never interrupted and a new radiological evaluation after 3 months showed a further increase in the lung lesions (Fig. 1b). We decided to stop the IFN therapy and the patient died 2 months later.
Figure 1. Progression of lung metastases is evident comparing the axial CT section at the beginning (a) and after 3 months (b) of IFN alpha 2b therapy.
We were consequently unable to confirm the encouraging report by Roozendaal et al. 3 and Kuriyama et al. 2. Although it was demonstrated that most solid tumors of childhood express IFN receptors, and that IFN treatment may inhibit their growth in vitro 4, other mechanisms—including immuno-mediated antitumor effects—may be relevant to its in vivo efficacy in ASPS. IFN may not be effective when the tumor burden is exceedingly high, as seemed the case in our patient by comparison with the imaging studies on the two reported cases in which this treatment was effective, although this is highly speculative. The role of IFN in ASPS deserves further study in order to better define its role and mechanisms of action.
REFERENCES
1Casanova M, Ferrari A, Bisogno G, et al. Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group. Ann Oncol 2000; 11: 1445–1449. CrossRef,PubMed,CAS,Web of Science® Times Cited: 182Kuriyama K, Todo S, Hibi S, et al. Alveolar soft part sarcoma with lung metastases. Response to interferon alpha-2a. Med Pediatr Oncol 2001; 37: 482–483. Direct Link:AbstractPDF(72K)ReferencesWeb of Science® Times Cited: 103Roozendal KJ, deValk B, ten Velden JJA, et al. Alveolar soft-part sarcoma responding to interferon alpha-2b. Brit J Cancer 2003; 89: 243–245. CrossRef,PubMed,Web of Science® Times Cited: 64Rosolen A, Todesco A, Colamonici OR, et al. Expression of type 1 interferon receptor in solid tumors in childhood. Mod Pathol 1997; 10: 55–61. PubMed,CAS,Web of Science® Times Cited: 15
2.1.
Alveolar soft part sarcoma with lung metastases. Response to interferon alpha-2a?
Kuriyama K, Todo S, Hibi S, Morimoto A, Imashuku S.
Med Pediatr Oncol. 2001 Nov;37(5):482-3.
To the Editor: We read with interest the report by
Pappo et al. entitled ``Alveolar soft part sarcoma in
children and adolescents: clinical features and outcome
of 11 patients'' [1]. Our experience with a boy with
alveolar soft part sarcoma (ASPS) with lung metastases is
relevant. The patient has remained in good health despite
persistence of lung metastases over 9 years from the
initial diagnosis and 6 years after discontinuation of
chemo-cytokine therapy. Review of the course of his
disease suggests a previously unknown susceptibility of
ASPS to treatment with interferon alpha (INF-a).
A previously healthy 8-year-old boy presented without
pain with an approximately 4-cm tumor on the upper and
interior side of his left knee on 5 February 1991. The
tumor was grossly resected and its histologic assessment
led to a diagnosis of ASPS. Macroscopic ®ndings at
surgery indicated that the tumor was not well circumscribed
and had invaded into the surrounding vastus
medialis muscle. At the time of diagnosis, chest radiography
and computed tomography (CT) scanning also
revealed multiple pulmonary metastases. The patient was
referred to the Kyoto Prefectural University of Medicine
for postoperative chemotherapy. His treatment consisted
of combinations of vincristine(VCR)/doxorubicin(ADR)/
cyclophosphamide(CPM), etoposide/cisplastin, CPM/
VCR/dactinomycin (Act-D), and ADR/VCR/ifosfamide.
This was followed by maintenance therapy consisting of
VCR, Act-D, and CPM for nine months between March
1991 and December 1991. The number and size of the
lung metastases remained stable throughout the course of
chemotherapy; after discontinuation of treatment, however,
the lung metastases gradually grew in size and
number. Consequently, in December 1992, the patient
was treated with INF-a -2a (3 million IU, i.m. three times
per week). After 6 months of interferon therapy (total
doses 216 million IU), the number of lung metastases had
decreased slightly, indicating a partial response (Fig. 1A).
At this point, however, the patient and his parents refused
to continue the treatment and the patient was lost to
follow-up age eleven.
On 25 February 2000, at 17 years of age, the patient
presented with chest pain to another hospital where
multiple lung nodules were seen on chest X-ray ®lms and
CT scans. Given his past history of ASPS, he was referred
to our hospital on 1 March 2000. We established there
was no recurrence at the primary site and that the patient
had been in good condition (Karnofsky score of 100%)
during the intervening years without receiving any
treatment. His complaint of chest pain was not related
to the original disease. When the present and past lung
CT scans were compared, we observed that his lung
metastases had decreased in number and diameter.
(Fig. 1B). His respiratory function was also found to be
within normal limits (100.0% vital capacity, 104.3%
forced expiratory volume1.0). As the patient had a good
quality of life, no organ dysfunction, and did not wish to
be treated, we decided to withhold further therapy but to
maintain close long-term surveillance.
Information on the precise long-term course to be
expected in a case such as ours is limited. (2,3) Our
survey of the literature revealed only three cases of ASPS
with lung metastases surviving longer than 3 years at
the time of those reports. These data must be coupled
with the fact the nodules in our patient grew after chemotherapy
and decreased in size only after the initiation
of INF-a-2a. Spontaneous remission of disease seems
a less likely explanation than ascribing the changes to
INF-a-2a.
The possible efficacy of INF-a-2a in treating ASPS
has not been previously reported, although experimental
studies have shown that INF-a is effective in treating
soft tissue sarcomas in general [4,5]. INF-a was found to
inhibit their in vitro proliferation in a manner that is
independent of their p53 status, although it did not induce
apoptosis in a soft tissue sarcoma cell line [4]. In
addition, Rosolen et al. [5] have shown that all solid
tumors that develop during childhood express INF-a
type 1 receptors and that treatment of these tumors with
INF-a inhibits their in vitro growth. Given these data on
the in vitro efficacy of INF-a, we speculate that the ASPS
in our patient may have responded to and been stabilized
by INF-a-2a, accounting for his long-term partial
remission without disease exacerbation. It is thus of
interest to know if ASPS expresses the INF-a receptor.
Despite its characteristic histologic features, ASPS remains
a tumor of controversial histogenesis and unclear
pathogenesis. In the past, immunohistochemical studies
have suggested that it may be both of neural and muscle
origin [2,3], and recent reports have confirmed its neural
origin by molecular and cytogenetic analyses [6]. Rosolen
et al. [5] have shown that neuro-endocrine tumors that
develop in childhood (i.e., neuroblastomas and primitive
neuroectodermal tumors) express the INF-a receptor and
are susceptible to the anti-proliferative effects of INF-a.
Further studies are necessary to con®rm the effectiveness
of INF-a in treating ASPS and to assess how this might be
related to the biologic characteristics and histogenesis of
ASPS.
Kikuko Kuriyama, MD*
Shinjiro Todo, MD
Shigeyoshi Hibi, MD
Akira Morimoto, MD
Department of Pediatrics
Kyoto Prefectural University of Medicine
Kyoto, Japan
Shinsaku Imashuku, MD
Kyoto City Institute of Health and
Environmental Sciences
Kyoto, Japan
REFERENCES
1. Pappo AS, Parham DM, Cain A, et al. Alveolar soft part sarcoma in
children and adolescents: clinical features and outcome of
11 patients. Med Pediatr Oncol 1996;26:81±84.
2. Ordonez NG. Alveolar soft part sarcoma: A review and update.
Adv Anat Pathol 1999;6:125±139.
3. Enzinger FM, Weiss SW. Alveolar soft part sarcoma. Soft Tissue
Tumors, 3rd Ed. St. Louis, 1995. P 13, and 1067±1074.
4. Brodowicz T, Wiltschke C, Kandioler-Eckersberger D. et al.
Inhibition of proliferation and induction of apoptosis in soft tissue
sarcoma cells by interferon-alpha and retinoids. Br J Cancer
1999;80:1350±1358.
5. Rosolen A, Todesco A, Colamonici OR et al. Expression of type I
interferon receptor in solid tumors of childhood. Mod Pathol
1997;10:55±61.
6. Chan AS, Squire JA, Thorner P et al. Molecular genetic changes in
alveolar soft part sarcoma. Pediatr Pathol Molecul Med 2000;18:
529±543.
2.2.
Interferon alpha for alveolar soft part sarcoma
Gianni Bisogno, Rosolen A, Carli M.
Pediatric Blood & Cancer
Volume 44, Issue 7, pages 687–688, 15 June 2005
To the Editor: Alveolar soft-part sarcoma (ASPS) is a rare malignant tumor for whom chemotherapy has little or no efficacy. Although we reported on some patients responding to conventional chemotherapy, results were ultimately disappointing if the tumor was not completely resected 1. Thus, new approaches are needed for patients with unresectable ASPS. The possible activity of interferon alpha (IFN) against ASPS has been previously documented 2. More recently Roozendaal et al. 3 described a partial remission induced by IFN 2b in a patient with ASPS. We therefore decided to use IFN in a patient with a chemoresistant ASPS.
A 7-year old girl presented in September 1996 with a rapidly-growing mass in her right buttock. A biopsy was performed confirming the diagnosis of ASPS. Staging revealed multiple lung metastases. Chemotherapy was administered according to the European MMT4 protocol without benefit. Further chemotherapy with topotecan and cyclophosphamide achieved no improvement and a very slow increase in the number and size of the pulmonary lesions was demonstrated on CT scan. Because the patient was otherwise in very good general condition, in March 1997 we agreed with the family to stop any further treatment, apart from irradiating the buttock lesion to diminish the local discomfort.
Towards the end of 2003, the patient's general condition suddenly deteriorated, with rapid weight loss (from 45 to 37 kg in approximately 1 month) and increasing respiratory insufficiency (oxygen saturation in the range of 91%–93%). New imaging studies showed an increase in the metastatic lesions (Fig. 1a) and revealed an intracerebral mass in the frontal lobe. With the family's and patient's consent, treatment with IFN 2b (3 × 106 IU s.c. day) was initiated. During the treatment, she suffered further weight loss and fever. Oral steroids (prednisone 25 mg daily) were given to ameliorate the symptoms. The fever disappeared and food intake improved. IFN treatment was never interrupted and a new radiological evaluation after 3 months showed a further increase in the lung lesions (Fig. 1b). We decided to stop the IFN therapy and the patient died 2 months later.
Figure 1. Progression of lung metastases is evident comparing the axial CT section at the beginning (a) and after 3 months (b) of IFN alpha 2b therapy.
We were consequently unable to confirm the encouraging report by Roozendaal et al. 3 and Kuriyama et al. 2. Although it was demonstrated that most solid tumors of childhood express IFN receptors, and that IFN treatment may inhibit their growth in vitro 4, other mechanisms—including immuno-mediated antitumor effects—may be relevant to its in vivo efficacy in ASPS. IFN may not be effective when the tumor burden is exceedingly high, as seemed the case in our patient by comparison with the imaging studies on the two reported cases in which this treatment was effective, although this is highly speculative. The role of IFN in ASPS deserves further study in order to better define its role and mechanisms of action.
REFERENCES
1Casanova M, Ferrari A, Bisogno G, et al. Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group. Ann Oncol 2000; 11: 1445–1449. CrossRef,PubMed,CAS,Web of Science® Times Cited: 182Kuriyama K, Todo S, Hibi S, et al. Alveolar soft part sarcoma with lung metastases. Response to interferon alpha-2a. Med Pediatr Oncol 2001; 37: 482–483. Direct Link:AbstractPDF(72K)ReferencesWeb of Science® Times Cited: 103Roozendal KJ, deValk B, ten Velden JJA, et al. Alveolar soft-part sarcoma responding to interferon alpha-2b. Brit J Cancer 2003; 89: 243–245. CrossRef,PubMed,Web of Science® Times Cited: 64Rosolen A, Todesco A, Colamonici OR, et al. Expression of type 1 interferon receptor in solid tumors in childhood. Mod Pathol 1997; 10: 55–61. PubMed,CAS,Web of Science® Times Cited: 15
Re: Why is it open
Hi everyone
I've had some time to reflect on our forum downtime and felt compelled to start a discussion on interferon as a treatment to ASPS as previously discussed
Wikipedia is a great source in my opinion for the person who may be without medical knowledge to begin with.
How cool would it be if we were able to discover that an antiviral medicine could cure ASPS?
Or maybe prevent it in the first place.
From all of our family to yours,
May your day be bright with hope and your nights be your comfort.
Debbie
http://en.wikipedia.org/wiki/Interferon_alfa-2b
I've had some time to reflect on our forum downtime and felt compelled to start a discussion on interferon as a treatment to ASPS as previously discussed
Wikipedia is a great source in my opinion for the person who may be without medical knowledge to begin with.
How cool would it be if we were able to discover that an antiviral medicine could cure ASPS?
Or maybe prevent it in the first place.
From all of our family to yours,
May your day be bright with hope and your nights be your comfort.
Debbie
http://en.wikipedia.org/wiki/Interferon_alfa-2b
Debbie