Childhood Cancer: Current Outlook (USPHS; American Radium Society, 1969)

Childhood Cancer: Current Outlook (USPHS; American Radium Society, 1969)


[Dr. John Pool:] Cancer is the most life-threatening situation that children face after neonatal period, except for accidents. At the 1968 meeting of the American Radium Society, one aspect of pediatric cancer is on the program for this reason. And also, because the treatment of solid tumors in children requires the joint services of surgeon, radiotherapist, and chemotherapist. And all three of these disciplines are represented in our membership. [Music] [American Radium Society] [Narrator:] As a professional education extension of the 50th annual meeting, the American Radium Society presents Childhood Cancer: Current Outlook. Participants are Dr. Lois Murphy, Chairman of the Department of Pediatrics at Memorial Hospital in New York; [Lois Murphy, M.D., Chairman, Dept. of Pediatrics, Memorial Hospital, New York] Dr. Lester W. Martin, Director of Pediatric Surgery at the Children’s Hospital in Cincinnati, Ohio; [Lester W. Martin, M.D., Director of Pediatric Surgery, Children’s Hospital, Cincinnati] Dr. Melvin Tefft, Radiotherapist and Chief at the Children’s Hospital in Boston; [Melvin Tefft, M.D., Radiotherapist-in-Chief, Children’s Hospital, Boston] and as moderator, Dr. Lemuel Bowden, Associate Attending Surgeon at Memorial Hospital in New York City. [Lemuel Bowden, M.D., Associate Attending Surgeon, Memorial Hospital, New York] [Dr. Lemuel Bowden:] Obviously in the time allotted, it would be impossible to comment even briefly on every type of solid malignant tumor of childhood. And we have agreed to confine our remarks to three of the most common ones, namely Wilms tumor, neuroblastoma, and embryonal rhabdomyosarcoma. The first case that I’d like to present is that of a nine-month-old baby boy who was noted approximately one month before hospital admission to have a slowly increasing abdominal girth with some distention of the superficial veins of the abdomen. But was not noted to have an abdominal mass until the day prior to admission. An immediate IVP was secured and this revealed the presence of a lesion of the right kidney. On the basis of this brief history, Dr. Martin, how would you go about managing this case? [Dr. Lester Martin:] This particular Wilms tumor is an ideal candidate for immediate object removal. The origin of the tumor from the lower part of the kidney tends to displace the renal pedicle upward somewhat and creates a bit more of a difficult operative approach for the surgeon. A point could be made for a thoracoabdominal approach in this particular child. Ordinarily as seen in the photograph, we prefer a transverse abdominal incision extending from one flank to the other, providing generous exposure and permitting early operation of the renal pedicle in the course of the operation. The location of the tumor within the kidney is of more importance to the surgeon than is the size. As seen in the next photograph, a particularly large tumor may be removed with relative ease. We feel that during the course of the operation the opposite kidney should be examined carefully. And as shown in the next photograph, the tumor on the opposite side may be particularly small and can be detected only by careful examination of all aspects of the opposite kidney. Bilateral involvement can be expected in approximately ten percent of the cases with Wilms tumor. We see that the operation is not complete until a thorough retroperitoneal [inaudible] assessment has been carried out. Occasionally the tumors spread to the retroperitoneal nodes prior to its spread to the lungs or elsewhere. [Dr. Bowden:] In an early case such as this one we have just detailed, do you feel, Dr. Tefft, that there is any case for radiation therapy, and possibly you’d also comment on the possibility of finding positive nodes or extrarenal extension at the time of surgical exploration and thereby, or in such an instance, a need for radiation therapy? [Dr. Tefft:] Well, in the younger child, especially a child under 13 months of age with a good overall prognosis, when the tumor is well-encapsulated and with no evidence of breaking the capsule, when there is no lymph node involvement and when there is no local vascular invasion, it is not our policy to use routine postoperative irradiation. However, when any of these other things are true; when these things are positive at the time of initial surgery or in the older child, when radiotherapy is used, the volume is carefully tailored to encompass the tumor-bearing tissue and to minimize the radiation to normal growth structures. The dose is consistent with both control of the tumor, and adjusted to the tolerance of normal tissues in the growing child. [Dr. Bowden:] Dr. Murphy, in an early Wilms tumor, what place is there for chemotherapy? [Dr. Lois Murphy:] A commonly accepted practice is to start a course of Actinomycin D on the day of operation. [Actinomycin D. day of surgery, invervals thereafter, concurrent irratiation +-] Many centers then give repeated courses of Actinomycin D at intervals of six weeks to two or three months, for one year. In our institution, the first two doses of Actinomycin D are given before operation together with two doses of radiotherapy over the tumor. Following operation, the remaining three doses of Actinomycin D is given and the radiotherapy of course continued. Repeated courses of Actinomycin D are given at intervals of two to three months for one to two years. [Dr. Bowden:] Of course, the idea behind such therapy is to prevent, we hope, the possibility of metastases. If these metastases, however, do occur in a Wilms Tumor, does this mean invariably a completely hopeless prognosis, Dr. Murphy? [Dr. Murphy:] No, there are many children who have received chemotherapy and radiotherapy for metastatic Wilms Tumor who had disappearance of these conditions and are well at the present time. [Dr. Bowden:] And is there any choice, do you think, between the chemotherapy and the radiation therapy in the management of such metastatic lesions? Or do you think it’s an entirely a combined, a combined endeavor? [Dr. Murphy:] I think that it should be a combined endeavor and of course the lesions may be excised surgically if they are discrete. [Dr. Bowden:] I was going to ask that of Dr. Martin. In the case of a solitary pulmonary metastasis from Wilms Tumor, do you think it’s very often that it is in fact solitary and that there is a place then for a surgical approach and segmental excision or lobectomy such as a solitary metastasis? [Dr. Martin:] In answer to your first question, I doubt that any of them are solitary. I suspect that most of them are multiple. We feel that the initial metastatic lesions can be treated by a combination of radiation plus chemotherapy. In occasional instance, one single lesion will recur following this course of treatment or will persist in spite of combined therapy. In that instance we do it by surgical removal. And in case another one should recur later on, we would remove that. We’ve had one child that has had five separate resections, removing only a small amount of lung tissue with each particular tumor, and the child has now had five, over five years since the last resection. [Dr. Bowden:] Dr. Tefft, would you care to comment on the management of metastatic Wilms tumor? [Dr. Tefft:] I would agree completely with Dr. Murphy that the first attack, and Dr. Martin, that the first attack would be a combination of radiotherapy and chemotherapy for the first evidence of metastasis. And certainly there are some children who do have solitary lesions that have survived after excision. I think the only point to make is when one does irradiate the lung for metastasis, one includes the total volume of both lungs, both apices and bases. [Dr. Bowden:] First case, being a relatively early example of Wilms Tumor, probably carries a very good prognosis with it. Unfortunately, this is not the case with all childhood tumors. And for the next case I’d like to present that of a seven-month-old baby girl who was found some two months before admission to the hospital to have likewise an enlarging abdomen and was noted to have an abdominal mass in the left upper quadrant shortly before admission, at the same time as a mass in the left groin was identified. The small mass in the left groin was removed for histologic study and proved to be metastatic neuroblastoma. An IVP [inaudible] revealed marked distortion of the left kidney position because of the presence of a large suprarenal mass with flaky calcification contained therein. Furthermore, a marrow aspiration in this child revealed the presence of extrinsic cells consistent with metastatic neuroblastoma in the marrow. Although the skeletal survey showed no definite evidence of bone destruction. In a situation of this sort, Dr. Tefft, would you comment as to how you would approach the problem therapeutically? [Dr. Tefft:] Well, in a child under one year of age, it is a distinctly better prognosis as compared to the older child with neuroblastoma. Given such evidence of disseminary disease, every attempt is made to control a disease that is encompassable by radiation and at doses tolerable to normal growing tissue. Therefore, after biopsy and possibly after surgical removal of the suprarenal primary, we would advocate irradiation of the suprarenal fossa and the node-bearing areas in continuity with this involved groin node. In advanced cases, in older children, when there is [inaudible] bone destruction by x-ray, we would deliver more modest curative doses of irradiation to the local site. [Dr. Bowden:] May I ask Dr. Martin, would you consider immediate surgery on the primary tumor above the left kidney, as a surgeon? Or would you prefer possibly to ask your radiation therapist colleague to give preliminary radiation therapy before attacking this surgically, or would you attack the primary tumor surgically at all? [Dr. Lester Martin:] In this particular child with evidence of metastatic disease in the bone marrow, we would be less, feel less urgent about object removal. If we had a negative bone marrow we would approach this aggressively and go immediately and remove the tumor. With a positive bone marrow, we would discuss it, the members of the team… and come to a decision and I suspect that we would probably remove the primary and then use combined radiation and chemotherapy. [Dr. Bowden:] Chemotherapy. And Dr. Murphy now. The question of the involvement of bone marrow has been utmost in the minds of all us in this particular patient. Would you comment on the significance of this and the treatment of this chemotherapeutically if you feel this is what should be now done. [Dr. Murphy:] I’d like to re-emphasize what Dr. Tefft said, that the prognosis in such a patient is grave but not hopeless. Neuroblastoma invading bone marrow has similarities to acute leukemia. Treatment should be selected to eradicate the extrinsic cell, thereafter normal bone marrow cells return. Neuroblastoma cells can be suppressed within a few days by the more vigorous chemotherapeutic agents. For example, a full dose of nitrogen mustard, a course of Actinomycin D., or high doses of cyclophosphamide. [Treatment: Nitrogen Mustard, Actinomycin D., Cyclophosphamide] There may result hyperuricemia; temporary, severe thrombocytopenia; and leukopenia. [Complications: Hyperuricemia, Thrombocytopenia, Leukopenia] To treat with these agents, the child needs to be prepared with good hydration and Allopurinol to prevent hyperuricemia. [Prepare with: 1) good hydration, 2) Allopurinal, Treat with: 1) Platelet transfusion, 2) (Isoluation)] In addition, if bleeding develops, platelet concentrates for supportive management may be required. If leukopenia is severe enough to lower the circulating granulocyte count to 1,500, a strict isolation to guard against infection may be necessary. And a normal bone marrow should regenerate within two or three weeks, following which a maintenance schedule of weekly, alternating doses of Cyclophosphamide and Vincristine can be used. [Alternating weekly doses: Cyclophosphamide, Vincristine] If one is not able to give heroic supportive therapy to such a patient, the latter two drugs can be used as the initial treatment and some good results have been observed with them. Some kind of chemotherapy certainly should be given for probably two years. The catecholamine excretion in the urine, as well as careful physical examination and serial bone marrow examinations, are helpful in determining activity of the neuroblastoma during the course of treatment. [Dr. Bowden:] Knowing of course, the hematopoietic depression effect in most chemotherapeutic agents, I think some practitioners might rightly fear the use of massive doses of any of the chemotherapeutic drugs if it appeared that the marrow had been largely replaced by extrinsic tumor cells. Would you comment on that? Do you think that is a contraindicating factor? The degree of marrow replacement in other words? [Dr. Murphy:] Well, this fear is certainly justified and we all share it. However, these neuroblastoma cells must be removed from the bone marrow, before there can be a remission and return of normal elements. So it takes a good deal of clinical judgment in determining how much of an agent a young patient can tolerate. It has something to do with the marrow reserve in a given child. [Dr. Bowden:] One comment I think certainly should be made with regard to neuroblastoma is the fact that in occasional instances there will be of course spontaneous regression of the tumor that is currently not completely understood. And for that reason too, I think that a totally hopeless prognosis should not be given, even in the advanced case such as we’ve just seen. So I’d like to go on to our third case if I may. This is that of a ten-year-old boy who three weeks prior to admission to the hospital was noted by his mother to have a painless mass in the right arm, affixed to the bone, or seemingly affixed to the bone and just distal to the elbow. He was seen by his local physician and promptly referred to the hospital on the suspicion that this might be a malignant tumor. At the time of admission, this mass was noted to be a fairly good size; five by three [inaudible] infiltrating mass. And at the same time, two or three definitely enlarged lymph nodes were identified in the axilla of that side. Assuming, as was the case in this patient, that the lesion proved to be an embryonal rhabdomyosarcoma, would you comment Dr. Martin, on your approach to this problem? [Dr. Martin:] This is a particularly difficult problem. The fixation of the mass to the bony structure of the forearm precludes local excision as a means of treating this as a [inaudible] surgical procedure unless we are quite radical in our approach. The spread to the axilla again means we must be more radical I think the only way we can approach this surgically other than to do the biopsy would be to do a forequarter amputation, which is certainly a rather mutilating operation for a small child faced with 65 more years of going around with the forequarter amputated. Now I would choose between that, or biopsy only and use the other modalities such as either radiation or chemotherapy as far as the definitive management. I believe the only operation we could do would be a forequarter amputation as a curative type of procedure. [Dr. Bowden:] I’m glad to hear you say that because I think cure is possible, even in this particular presentation by such a radical surgery. But I’d like to ask Dr. Tefft if he feels there’s any place for radiation therapy in the management of this particular patient. [Dr. Tefft:] Well, as Dr. Martin has indicated this is indeed a very difficult problem. Irradiation at high dose, especially when combined with chemotherapy, has resulted in marked regression of some of these lesions. But when the disease can be removed surgically, lest there be local recurrence and one cannot be sure of total eradication of all cells in this particular region, it might be as well to do such a radical procedure as Dr. Martin has indicated. In other areas such as the nasopharynx when total surgical extirpation is usually not possible, then radical high dose irradiation when combined with chemotherapy has indeed resulted in the survival in some patients. [Dr. Bowden:] Dr. Murphy, would you comment on the seeming influence of primary location of the embryonal rhabdomyosarcoma and prognosis or possibly in the treatment? [Dr. Murphy:] Embryonal rhabdomyosarcoma may arise in soft parts of the head and neck, the genitourinary tract, the extremities or the retroperitoneal areas. [Head and neck, Peripheral soft parts, Bladder-Prostate-Vagina, Abdomen] The prognosis is somewhat better when the origin of the tumor is in the head and neck area. Chemotherapy of choice for embryonal rhabdomyosarcoma is Actinomycin D, Cyclophosphamide and Vincristine also has some beneficial effect. [Actinomycin D., Cyclophosphamide, Vincristine] This tumor invades the bone marrow and therefore marrow examination needs to be carried out before the chemotherapy is selected. [Dr. Bowden:] And in this particular instance may I ask, assuming that a forequarter amputation were done, would you recommend in the post-operative period that any you know, so-called suppressive chemotherapy be administered? This is a leading question but I’d be interested in your thoughts on that. [Dr. Murphy:] Well, the frequency with which this tumor metastasizes widely, including replacing the bone marrow, I think it’s worthwhile to consider so-called prophylactic chemotherapy in this condition, give courses of Actinomycin D or perhaps I think this is a good situation to use combined chemotherapy. There’s been some interest in Actinomycin D together with Vincristine and we’ve given Actinomycin D together with Cyclophosphamide in repeated courses in an effort [inaudible]; [Dr. Bowden:] [Inaudible] [Dr. Murphy:] in order to continuously suppress the tumor. [Dr. Bowden:] I see. [Dr. Murphy:] Certainly along with the x-ray therapy and surgery. [Dr. Bowden:] Dr. Martin, would you agree with that? Or did you have any other comments? [Dr. Martin:] No, I think I’d agree with that. In one particular child with rhabdomyosarcoma of the orbit with metastasis to the local area was treated with a radical operation excising the orbit, primary occlusion of the tissues. The metastatic lesions were removed by only local removal and the child received [inaudible] radiation to the neck and the nodes disappeared completely. It’s only been 19 months since the procedure. We still feel that that the prognosis is poor, but such a hopeful occurrence makes us feel as though it’s not an entirely hopeless disease. [Dr. Bowden:] I think many of us have the impression that possibly, embryonal rhabdomyosarcoma arising in the head and neck area may be a little more responsive to radiation therapy than such tumors arising elsewhere, and may have a little better prognosis, although this is very difficult to prove statistically. Would you care to comment on that, Dr. Tefft? Do you think they have a somewhat better prognosis? [Dr. Tefft:] I think that I agree that it is difficult to analyze it, particularly as the patient numbers are so small. But my impression is that this is indeed true. [Dr. Bowden:] Are there any other comments any of you would care to make about this case? If not, in summary then, I think we have presented three fairly typical cases of solid malignant tumors in childhood and their treatment has been most ably discussed by my panel members here. I think it is worthwhile to note that current practice favors the combined therapeutic approach for which the capabilities of several medical disciplines, surgery, radiation therapy, and chemotherapy, may be and frequently are utilized in the management or in the total care of these patients. Childhood cancer is happily not common, but does rank as the second most frequent cause of death in children past the neonatal period. With early diagnosis and with skilled and dedicated treatment however, a favorable outcome may be anticipated in a substantial number of these patients. [Music] [American Radium Society] [Narrator:] This program, Childhood Cancer: Current Outlook, was produced by the American Radium Society during its 50th annual meeting in Miami Beach, Florida, April, 1968. [Music]

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