Principles and Results of Palliative Radiotherapy in Nonresectable Cancer

Principles and Results of Palliative Radiotherapy in Nonresectable Cancer RALPH PHILLIPS, M.D., F.R.C.S.

SIMPLY stated, there is really only one principle in radiotherapy-to damage or destroy the cancer without injury to the host; and this possibility exists because many malignant cells appear to be more radiosensitive than normal cells. Radiotherapy began and developed as an empirical art based on this differential radiosensitivity, and to this day is dominated by the concept of a tumor lethal dose. The search for this ideal tumor lethal dose which will destroy every malignant cell without undue damage to the patient has produced the multifarious techniques of radiotherapy in use today, with notable improvements in precision and results. Such an approach to radiotherapy is nevertheless an oversimplification, since it fails to take into account the environment in which the malignant cells may be multiplying, static or regressing. For example, a primary tumor and its metastases do not have a constant "tumor lethal dose," bone metastases are usually much more "radiosensitive," and lymph-node metastases often less "radiosensitive" than the parent tumor. Still more variable is the tumor lethal dose from one patient to another, when not only the local environment but also the general environment are different. Biological control of a tumor by its host is no longer a theory, and by analogy the response of the body to irradiation of a tumor is probably as important a factor in the control of malignant disease as the direct injury or destruction of cancer cells, because these systemic alterations also change the micro-environment in which the interactions between malignant cells and absorbed radiant energy occur. The initial change when radiation is absorbed is at the atomic level, and is called excitation; electrons escaping from atoms produce molecular ionization. The ensuing physical, chemical and biological changes are exceedingly complex and the relative order of effects such as chromoFrom the Department of Radiation Therapy, Memorial Hospital. 807

Ralph Phillips

808

some breakage, cell hydrops, and alterations in enzyme systems (especially those concerned in nucleic acid synthesis), is uncertain. However, the long series of chain reactions initiated by ionization ultimately become significant in three main ways: (1) death of malignant cells during mitosis; (2) inhibition of mitosis so that malignant cells differentiate into mature types; and (3) an aseptic inflammatory reaction proceeding to replacement fibrosis in and around the irradiated tumor. A cancer may be nonresectable in the absolute sense that its removal is incompatible with survival, or in various relative senses that render its removal unwise or unnecessary. Unnecessary excisions are outside the title of this paper, implying differences of opinion and approach between surgeons and radiotherapists, as for example in carcinoma of the vocal cord or cervix uteri; such differences, however, tend to disappear in those tumor clinics where joint consultation and teamwork are the rule. Unwise excisions occur mostly in cases of borderline operability, where the risks of local recurrence in the operative field are weighed against the prospects of palliation or even cure; recurrent nodules in the skin of the chest wall after radical mastectomy, or massive recurrence in the neck or pelvis after radical extirpations are examples. Another class of unwise excisions compr;se cases in which widespread metastases appear shortly after operation. Both surgeons and radiotherapists would like their propter hoc judgments to be better correlated with the post hoc course, but radiotherapy has one advantage over surgery in that it is not fully committed at the outset; during the course of irradiation when it extends over several weeks, changes in the tumor can be observed and the plan of treatment modified accordingly from palliative to radical or vice versa. Moreover,) a radiotherapy failure, complete or partial, may still be rescued by surgical intervention; whereas the reverse is often difficult because the cancer-invaded and altered normal tissues after operation may not tolerate an adequate radiation dose. It is desirable to make the definition of palliation as precise as possible, so that: A. The therapeutic aim is definite, not vague. B. The anatomical site to be irradiated is defined. C. The probable radiation dose required and the overall time in which it is to be given can be planned. D. The best technique of irradiation can be selected. E. The results of therapy can be evaluated, as: (1) disappearance of disease, and for how long. (2) arrest of spread of disease, and for how long. (3) relief of specific symptoms. DEFINITION OF THERAPEUTIC AIM

1. In Patients with Symptoms

The commonest indication for palliative radiotherapy is pain. If the cause of the pain can be accurately diagnosed, irradiation directed to its

Radiotherapy in N onresectable Cancer

809

origin will produce relief in the majority of cases. To illustrate what is meant by accurate diagnosis, take a patient who had a left radical mastectomy two years ago and now eomplains of pain below the right breast. There are numerous possible causes for this pain: it may not be related to cancer at all; it might be due to a new cancer in the right breast; or it may be due to metastatic cancer in the ribs, pleura, lung, liver, dorsal vertebrae, internal mammary lymph nodes, posterior mediastinum, spinal canal or pericardium. The patient's account of her pain together with judicious questions will eliminate some of these causes; physical examination will indicate the probable cause, and radiographic and other laboratory studies will precisely define it. As with pain, so with other symptoms~cough, dyspnea, edema, ascites, tenesmus, bleeding, discharge, obstruction, paresthesiae, paresis~accurate diagnosis is the essential prerequisite to successful therapy. When a patient has multiple symptoms, the predominant symptom is selected for relief first, and affords a guide to the advisability of further therapy for other symptoms. 2. In Patients Without Symptoms

An asymptomatic patient with a nonresectable cancer poses a difficult problem when the tumor is still localized and yet the statistical probability of cure is slight. The advisability of radiotherapy for the prevention of symptoms which may arise in the future, or for the prolongation of useful life, or for delaying the appearance of metastases, depends mainly on the type of cancer; for example, in cancer of the lung the response to irradiation is so uncertain and the future course of the disease (particularly as regards distant metastases) so different that it will generally be wiser to withhold treatment until symptoms appear; on the other hand, in chondrosarcoma of the pelvis the probability of growth arrest for months or even years is sufficiently high to make irradiation advisable even in the absence of symptoms. 3. For Improvement of Working Capacity

Patients with various forms of malignant disease may have no specific symptoms but only complaints of a general nature such as tiredness, weakness, inability to do a full day's work, and so on; such complaints may be the initial symptom in malignant lymphoma, and are usually greatly relieved by appropriate therapy, e.g., by irradiation of the spleen in chronic myelocytic leukemia, or of mediastinal lymph nodes in Hodgkin's disease. General symptoms without any localized symptom are much less common in carcinoma, and are usually due to metastases rather than to the silent primary tumor, e.g., retroperitoneal lymph node metastases in seminoma testis, bone metastases in carcinoma of the kidney, or adrenal metastases in -bronchogenic cancer.

Ralph Phillips

810 4. For Prolongation of Life

It is all too often assumed, though perhaps tacitly rather than expressed, that the main purpose of radiotherapy in nonresectable cancer is the prolongation of life; yet in most cases there are no reliable means of predicting how long it would be without radiotherapy. Prolongation of life without some restoration of function or relief of suffering can hardly be termed palliation, though in exceptional circumstances it may be of importance. Prolongation of life cannot be the aim of palliative radiotherapy, but results so to say as a bonus from the relief of distressing symptoms and restoration of function through arrest of tumor growth. 5. For Psychological Reasons

Almost as hardy as the idea of prolonging life is the recommending of radiotherapy because "nothing else can be done." There is always much that can be done for the physical, psychological and spiritual comfort of a patient with incurable cancer, and very rare indeed is the occasion when the use of irradiation with no intention of affecting the cancer is either necessary or justifiable. DEFINITION OF ANATOMICAL SITE FOR InRADIATION

It is a principle in radiotherapy to irradiate as little normal tissue as necessary for two main reasons: (1) The larger the volume irradiated, the more frequent and the more severe are debilitating systemic effects, e.g., nausea, anorexia, leukopenia, anemia. (2) The larger the volume irradiated, the smaller is the total radiation dose which can be tolerated by the normal tissues, which may thus limit the tumor dose to an insufficient and inefficient level. In defining the therapeutic aim, the anatomical site of the tumor causing the symptom to be alleviated is also necessarily defined. In many cases it is desirable in palliative radiotherapy to restrict the volume irradiated to this turn or, ignoring both its nearby and more distant metastases; for example, a patient with a tumor blocking the right main bronchus was found on roentgenography to have a completely opaque right hemithorax but without any mediastinal shift; his main symptom was an intractable cough, and the biopsy was reported as epidermoid carcinoma; the volume irradiated was therefore limited to the hilum of the right lung, because this was the most likely site of origin of his cough, and because the effective tumor dose for epidermoid carcinoma is seldom less than 4000 r, which is a dose above the tolerance level for the lung as a whole. In this particular case, the upper lobe showed reaeration when the tumor dose had reached 3600 r, and the whole lung became aerated at 4500 r when the patient coughed up a large piece of tumor. In other cases, however, it may be preferable not to restrict the irradi-

Radiotherapy in N onresectable Cancer

811

ation to the symptom-producing tumor; for example, the symptoms may indicate a cerebral metastasis in the inferior portion of the precentral gyrus, but brain metastases are so often multiple that the probability of further symptoms from other metastases is high, so that it is wiser to irradiate the whole brain; this is possible because the tumor dose required is about 3000 r, which is well below the tolerance of the normal tissues in the ar~a. RADIATION DOSE, FRACTIONATION AND OVER-ALL TIME

The accumulated experience of 60 years of radiotherapy offers an empirical dosage scale for the cure of various types of cancer. Experience offers much less guidance on the time factor, that is, on the rate at which the dose is given. The time factor comprises three independent variables: (1) intensity or dosage rate-roentgens per minute or per hour; (2) interval between successive doses-daily, twice daily, every other day, etc.; and (3) length of course of treatment-five days, two weeks, two months, etc. The possible dose-time combinations are thus almost infinite, but in practice there is not only an economic limitation, but also ill-defined limits dependent on the ratio of normal-tissue injury to tumor inhibition. Injury to normal tissue seems to be lessened by prolonging the time factor, whereas injury to malignant cells depends mainly on the dose of radiation. Thus, in curative radiotherapy there is a trend towards more prolonged over-all time (often accompanied by somewhat higher total dose), but in palliative radiotherapy the remaining life expectancy is an additional and important consideration. In treating a bone metastasis, for example, pain may be completely relieved by 1000 r; if the patient has visceral metastases, treatment may well stop with the relief of pain, since it may not recur during the remaining life; if other metastases are confined to the skeleton, the dose might be continued to 2000 r, with the expectation that growth arrest will last for a year; if it is a solitary metastasis, the dose might well be 3000 r; aiming at a prolonged local "cure." Similar reasoning enters into all palliative radiotherapy, and since also there are very few statistical evaluations of the results, there are no generally accepted dosage scales or time factors for palliation comparable to those curative techniques which can to some extent be judged by their five-year disease-free survival rates. Palliative radiotherapy is thus much more subject to individual experience and judgment. SELECTION OF METHOD OF IRRADIATION

The radiotherapeutic principle of producing the requisite degree of tumor regression with minimum risk to normal tissues; least discomfort to the patient, and minimum exposure of personnel determines the best

812

Ralph Phillips

method of treatment. For example, a small group of skin nodules near the scar of a radical mastectomy may be treated effectively with a dose of about 3000 r by a radium mold, a radioactive phosphorus beta-ray applicator, a million volt electron beam, or a low voltage (40 to 100 kv.) x-ray beam; the first two are eliminated as involving unnecessary exposure of personnel, and the third is unlikely to be available. The low voltage x-ray is preferable to "deep x-ray therapy" at. 180 to 250 kv., because the latter beam penetrates into the lung and produces radiation pneumonitis, so that an unnecessary risk is taken of normal tissue damage which may progress to pulmonary fibrosis. A more difficult example is recurrent disease in the pelvis causing pain, discharge and some obstruction to ureters or bowel; whether the primary carcinoma was in the rectum, ovary, uterus or bladder, the minimum palliative dose is likely to be about 4000 r, and for more lasting palliation 6000 r may be desirable; with the generally available deep x-ray therapy (250 kv.) skin tolerance limits the tumor dose to about 3500 r, but with supervoltage (1000 kv.) the skin is no longer the limiting factor and the tumor dose can safely be raised to 4500 r and is now limited by the visceral tolerance. With a precise rotation technique using telecobalt or supervoltage apparatus, tumor doses in the 6000 to 8000 r range are possible, and hitherto "radioresistant" tumors such as chordoma become amenable to palliative therapy. Roentgen rays are by no means the only agent to be considered; for example, the implantation of radon seeds in a nonresectable bronchogenic cancer at the time of surgical exploration is often a valuable palliative measure, and has a further advantage in facilitating tumor localization for subsequent x-ray therapy. Intracavitary radium applicators are especially useful for cancer involving the uterus and vagina, and radium needle implants for carcinoma of the tongue. For malignant pleural and peritoneal effusions a colloidal solution of radioactive gold is effective, and other radioactive isotopes have sound claims as the agent of choice in particular situations. These few examples suffice to show that the same wide selection of radiation sources and therapeutic techniques is just as necessary for palliative as for curative radiotherapy. Unfortunately, there are not many hospitals with all these facilities, so that doctors in general are not aware of how much could be done for their patients with cancer. I must emphasize that successful radiotherapy requires good tools as well as skilled therapy. For example, the results of "supervoltage" irradiation cannot be obtained with ordinary "deep x-ray therapy" apparatus, any more than those of deep x-ray could be gotten with the 120 kv. apparatus of an earlier day. For each million of population, there are about 1000 patients per annum requiring radiotherapy; almost half of those would fare better with supervoltage than with deep x-rays, so

Radiotherapy in N onresectable Cancer

813

that there should be at least 100 supervoltage or telecobalt apparatus in the U.S.A. instead of the score at present in use. RESULTS OF PALLIATIVE RADIOTHERAPY

In Table 1 the common sites of carcinoma and approximate five-year survival rates following radical radiotherapy as the primary method of treatment are given, and these indicate the likelihood of palliation when the disease is too advanced to justify an attempt at cure. The commoner symptoms are listed and the percentage of cases in which relief may be expected to follow palliative irradiation estimated, together with how long it may be expected to last. Then some guidance is offered on the preferred method of irradiation and tumor dose, but without implying that palliation cannot be obtained at lower dose levels or by other radiation techniques. A similar simplified summary of the palliative possibilities for distant metastases of carcinoma is offered in Table 2. In Table 3 lymphomas and sarcomas are listed in order of radiosensitivity; in the radiosensitive group it is usually justifiable to aim at cure of previously untreated cases, since this gives the best assurance of prolonged local control. For example, a girl aged 11 with Hodgkins' disease had developed lymph nodes in the neck, mediastinum and right axilla; a mediastinal tumor dose of 3000 r was given in ten days in January 1952, and although the pelvic lymph nodes required treatment in 1954 and the spleen in 1955, there has so far been no recurrence in the mediastinum. The simplified presentation in all three tables does not take into account the wide variations in the natural history and biological characteristics of malignant disease wherever situated. It is taken for granted that the experienced radiotherapist considers these factors in planning treatment, and that he takes advantage of all the aid which internists can g;ive in the total care of patients, particularly with regard to nutrition, hormone therapy, chemotherapy, control of infection, management of associated cardiovascular and metabolic disorders, and rehabilitation. The radiotherapy of cancer requires the successful synthesis of much knowledge and experience from the fields of oncology and pathology, of medicine and surgery, of radiation physics and radiobiology, of endocrinology, chemotherapy and biochemistry. It is impossible for such a combination to exist in one individual, so that the essence of successful radiotherapy is cooperation. It is not enough to "refer" a patient for radiotherapy; there must not only be initial consultation, but continuous consultation. Although two out of every three patients with cancer require radiotherapy sooner or later in their course, so that the radiotherapist inevitably becomes something of a cancer specialist, radiotherapy is still only a part of their "total care;" and the success of this part depends in no small measure on the care of the whole.

Ulceration

Inability to eat, pain and salivation Pain

Dysphagia

Dysphagia, salivation, substernal pain

Obstruction, vomiting

70

30

10

5

0

Tongue, tonsil

Pharynx Postcricoid

Esophagus

Stomach

MAJOR SYMPTOMS

Skin, lip

SITE

FIVE-YEAR SURVIVAL (per cent of all cases treated)

RADICAL RADIOTHERAPY

Supervoltage or telecobalt Deep x-ray Telecobalt rotation Deep x-ray Supervoltage Deep x-ray rotation

3-18 3-6 3-12 3--6 2-24

3--6

60 50 30 30

65

20

Betatron x-ray Supervoltage

Low voltage x-ray Radium-needle implant

6-60

Apparatus in Order of Preference

4000

4000

5000

6000

4000

5000

3000

5000

4500 5000

4 4

7 6

4

4

3

6

4 1

Tumor Over-all Dose Time (r) (weeks)

RADIATION TECHNIQUE

70

SYMPTO- DURATION MATlC OF RELIEF RELIEF (per cent (months) of cases)

PALLIATIVE RADIOTHERAPY

PRIMARY CARCINOMA

Table 1

~

Transverse colitis

i

~

~

Fibrosis with stenosis, perfor- >'l ation into mediastinum or ~ ~ aorta, hilar fibrosis

Anorexia

Dry mouth, loss of taste occasional hemorrhage

RADIATION REACTIONS AND POSSIBLE COM1PLICATIONS

~ ~

Aphonia, dyspnea, soreness

Dyspnea

Atelectasis, cough, dyspnea, mediastinal pain

50

10

3

Vocal cords and supraglottic

Subglottic

Bronchus, main divisions

---

Abscess, fever, visceral pain

Pain, obstruction, cranial nerve palsies

30

Nasopharynx

-

Pain, nasal obstruction Ocular palsies

25

Nasal sinuses

Bronchus, peripheral

Pain, discharge, ulceration

20

Anal canal

Tenesmus, pain, discharge, obstipation

I Back pain, obstruction common duct

10

----------

0

Rectosigmoid

Pancreas

Supervoltage Deep x-ray Deep x-ray Telecobalt Deep x-ray Supervoltage Deep x-ray

Supervoltage

3-24 6-36

6-36 3-12 2-12

6-18

30

50

60

25

70

70

Supervoltage or telecobalt Deep x-ray

Supervoltage

Supervoltage

Betatron x-ray Supervoltage

6-24

3-18

6-30

1-18

60

50

60

25

4 4

6

4000 3500

5000

6 6

5000 6000

5

5 3

4000 3000

4000

4

5

4

6

4 4

3500

4000

4000

6000

5000 4000

Lobular fibrosis

-

----

Esophagitis, hilar fibrosis

Laryngeal edema

Laryngeal edema, chondronecrosis

Loss of taste, dry mouth and throat, anorexia

Conjunctivitis, loss of taste, late radiation cataract

Moist desquamation in perineum

Proctitis, cystitis

Enteritis

....... ~

00

""'

~

~ ;;:l

~

SO"'

("")

<:\)

""'~

~ ;;:l

~.

~

~

So

~.

>::l R.

~

IV)

Hemorrhage, discharge, abdom. pain

rhage, pain, ureteral obstruction

-----52 (in Stages I and Il) Discharge, 20 (in Stages III and hemor-

50

lymphatic obstruction, brachial neuritis

50 (in Stages I and Il) Ulceration,

(per cent of all cases treated)

MAJOR SYMPTOMS

cases with postop. irradiation)

swelling, pain, chronic intestinal obstruction

------ ---------- -----30 (includes operated Abdominal Ovary

Cervix uteri

------

Corpus uteri

Breast

SITE

FIVE-YEAR SURVIVAL

RADICAL RADIOTHERAPY

50

70

70

65

(per cent of cases)

SYMPT0MATIC RELIEF

Supervoltage Deep x-ray

Apparatus in Order of Preference

3-24

IV survive 5 years)

8% Stage

III and

Supervoltage

deep x-ray or supervoltage

6-60 Intracavitary (25% Stage radium plus

4000

6000

6000

4500 3500

5

5

5

4 4

Tumor Dose Time (r) (weeks)

RADIATION REACTIONS AND POSSIBLE COMPLICATIONS

~

~ <:::

~

.......

00

Co

.[

'"v ;;::,::::..

- - - - - - - - - - - - - ;;::,Enteritis

Cystitis, proctitis, hydronephrosis, pyelonephritis, vaginal atresia

Cystitis, proctitis

Patchy moist desquamation, peripheral pneumonitis

I Over-all I

RADIATION TECHNIQL"E

RADIOTHERAPY

Intracavitary radium plus years surdeep x-ray or vival) supervoltage

6-60 (22%-5

6-36

(months)

DURATION OF RELIEF

P ALLlATIVE

Tahle 1 (continued)

35 (with orchidec-

Testis, embryonal carcinoma

Backache (lumbar nodemetastases)

Perineal pain, frequency, tenesmus

Strangury, frequency, painful cystitis

Backache, hematuria

Superior mediastinal compression

Few or 0

Thyroid, carcinoma simplex

---

Tumorpressure

35

Thyroid, papillary or alveolar

Backache tomy and "prophy(lumbar lactic irradiation) node metastases)

tomy and "prophylactic" irradiation)

90 (with orchidec-

Few or 0

Prostate

Testis, seminoma

Few or 0

35

0

Urinary bladder Papillary Infiltrating

Kidney

1-6

6-36

60 30

3-24

survival)

Interstitial radioactive gold by injection Deep x-ray

Intracavitary radioactive isotope Supervoltage rotation or telecobaIt rotation

Supervoltage Deep x-ray

I

Deep x-ray

Deep x-ray (Sometimes radioactive iodine)

Supervoltage

12-60 Deep x-ray (40% 5 yr.

6-18

6-30 2-9

6-24

40

100

50

60 20

40

3500

3000

4000

2500

3000

-

4000

6000

4000 3500

Enteritis, glomerulonephritis

3

3

4

4

4

-

4

treatments

I

Laryngeal edema, tracheitis, pharyngitis, hemorrhage

Pharyngitis

Enteritis, nausea

bladder

6 weekly Cystitis, irritable contracted

4 4

00 ''<

~

~

~

1;'"

O"'

S-

~

Cl> C':>

~ ~

;;.

~

~

So

~.

2-

;::,

Ralph Phillips

818

Table 2 METASTATIC CARCINOMA

PALLIATIVE RADIOTHERAPY

METASTATIC

SITE

Bone, 08teolytic Bone, 08teo-

SYMPTOMS

Pain, disability, fracture As above

plastic ------Paralysis, Brain stupor, incontinence

Liver

Pain, fever. jaundice, anorexia

------ ----Lung

Lymph nodes (fixed)

Dyspnea,

cough, hemoptysis

Relief (per cent of cases)

Duration of Relief (months)

Method ill Order of Preference

80

3-60

Deep x-ray

2000

2

40

2-24

Deep x-ray

3000

3

Skin erythema

70

2-30

Deep x-ray

3000

4

Temporary epilation

65 40 50

2-12

Supervoltage x-ray

3000

1

Nausea and vomiting in half the

Tumor

Dose (r)

Overall Time (weeks)

cases

30 50 70

2-6

50

3-60

Supervolt. or deep x-ray

2000

7000

2

-

20

2-6

3000

3

Eye, orbit

Paresis, visual loss

70

6-60

Deep x-ray

2500

2

Peritoneum

Ascites

50

2-12

150 mc.

40

2-12

IntraperitoneaI radioactive coli. gold Supervolt. or deep x-ray

3-24

Pleura.

Effusion

60 50

Usually Intrapleural no recradioactive urrence coli. gold Supervolt. or deep x-ray

Transient pneumon-

itis

Radon seed implant when possible Supervolt, or telecobalt Deep x-ray

Pain and pressure

Radiation Reactions

4500

4

-

3000 100 mc. 2000

Ulceration must be avoided

Late cataract can often be avoided Nausea

4 -

2

Diarrhea Transient pneUffionitis

Table 3 LYMPHOMA, SARCOMA AND 1l!SCELLANEOUS CANCER

Dose (r)

lellkcmia

(Recurrent or DiHscrninated Disease)

(Localized DiHcase)

Tllmor

A('ute

PALLIATIVE RADIOTHI';RAP¥

RADIcAL HADIOTHEUAP'{

LESION

f)-year Survival Symptoms Likely (per to be Relieved

Over-all Time (weekF)

-

cent)

-

-

Infiltration of meninges, liver, kidneys, etc,

Multiple

myelollla

-

-

TUlTlOr

Dose (r)

Over-all Time (weeks) 1

Bleedinl/:

Anemia

-

Pain, fracture

1500

1

1000

2

2500

3

20

Pain, intestinal obstruction, cough, proptosis

Hetilloblastoma

2500

1

70

Pain, ulceration. intracranial extension

lIodgkin's disease

3000

1

30

Swelling, pain, pressure, itching

1500

2

Lymphosarcoma

3000

1-3

50

Swelling, pain, pressure

500 to 2000

1-3

Ewing's

3500

3

5 to 10

Pain, cough, proptosis. paraplegia

1000 2000

1 3

Pain, cough, pressure

2000

3

tumor

Heticulumcell sarcoma Bone Soft tissues

Unlikely to Respond

100 to 500

NCllfO-

blastoma

Complications

------BlindIless 2 2000

Leukosarcoma. leukemia Cachexia

3500 4000

3 4

3.'; ?

-

Varies widely

Embryonal tumors in children, e.g., "'Tilms' -----Brain tu mars in children, e.g., medulloblas-

3500

3

15

Abdominal pain, dyspnea, cough Bone pain

2500 1800 !OOO

1

Raised intracranial tension, spinal cord compression

2000

3

Transverse myelitis if it has Leen presell t more than 4-7 days

Lipo-, myxo-, leiomyo-, fibrosarcomas

~OOO

:l 2

Respiratory failure

torn a

Chondrosarcoma Osteosarcoma

3000 to 5000

4-6

4000

G

o to 30

3-5

Not unusual

Pain, pressure, hemoptysis

3000 2000

A few

Pain, pres,,
to 5000

?

----------5000 6

6000

7

Meningioma

5000

4

-

Astrocytoma

6000

6

-------

Rhabdomyosarc. Glioblastoma multo

---

~

--

---

3 2

Intestinal obs.truction, renal failure

0

Pain

FUllgation, locomotor symptoms. dYl5pnea ------ - - - - 3000 3 -------3000 3 -------Ulceration 1 2000

0

Headache

4000

Rare

Headache Headache

819

3000 4000 2000

3 4 2

4

Paralysis, apha~ia

Ralph Phillips

820 REFERENCES

1. Ackcrman, L. V. and del Regato, J. A. Cancer: Diagnosis, Treatment and Prognosis. St. Louis, C. V. Mosby Co., 1947. 2ud Ed. 1954. (A comprehensive text which maiutains a high standard throughout.) 2. Bouehard, J.: Skeletal Metastases in Cancer of Breast; Study of Character, lneidence and Response to Roentgen Therapy. Am. J. Roentgenol. 54: 156171,1\)45. 3. Cade, S.: Malignant Disease and Its Treatment by Radium. Bristol, John Wright & SOIlS Ltd., 4 Vols., 1952. Baltimore, Williams & Wilkins Co. (An outstanding text for dinicians.) 4. Cm'ling, E. R., Smithers, D. W. and Windeyer, B. W.: Practice in Radiotherapy. London, Butterworth & Co. Ltd. St. Louis, C. V. Mosby Co., 1955. (Statistics of results of radical radiotherapy are an especially valuable feature.) 5. Chao, J., Phillips, R. and Nickson, J. J.: Roentgen-Ray Therapy of Cerebral Metastases. Callcer 7: 682, 1954. 6. Hodges, F. J., Lampke, I. and Holt, J. F.: Radiology for Medical Students. Chicago, Year Book Publishers, 1947. 7. Holmes, G. W. and Schulz, M. D.: Therapeutic Radiology. Philadelphia, Lea & Febiger, 1950. 8. Karnofsky, n. A., Myers, W. P. and Phillips, R.: Treatment of Inoperable Pulmonary Cancer, Primary and Metastatic. Am. J. Surg. 89: 526, 1955. 9. Levitt, W. M.: Handbook of Radiotherapy for Senior and Postgraduate Students. London, Barvey & Blythe Ltd., 1952. (A masterly condensation for every doctor ill nontechnical language.) 10. 1'11(,k, G. T. and Livingston, E. M.: Treatment of Canccr and Allied Diseases. I\ew York, Paul B. Hoeber Inc., 3 Vols., 1940. (A reference book for surgeons and oncologistR. The radiotherapy is now somewhat outdated.) 11. Paterson, R.: Treatment of Malignant Disease by Radium and X-ray. Baltimore, Williams & Wilkins Co., 1948. (The outstanding text for radiotherapists, but no dillical statist.ic~) 12. Phillips, R, Karnofsky, D. A., Hamilton, L. and Nickson, J. J.: Roentgen Therapy of Hepatic Metastases. Am. J. Roentgenol. 71: 826, 1954. 13. Phillips, R: Indications for Supervoltage Jrradiation. Med. Ann. Dist. Columbia 24: 53.'), 1955. 14. Phillips, Rand Dargeon, H. W.: Radiotherapy in Tumors of Childhood ..1. Pediat. 44: 448, 1954. 15. Portmann, U. V.: Clinical Therapeutic Radiology. New York, Th08. Nelson & SOIlS, 1\)50.